Natural Healing for Thrombocytopenia

Conquer Low Platelets

Alternative And Natural Therapies For Itp (idiopathic Thrombocytopenia Purpura). Live Free From Itp. Complete Program To Increase Platelets. This Is What You Will Learn With this Guide: The Two Herbs That can help bring up your platelets. The Two Vitamins needed to keep those platelets from dropping. What foods may cause your platelets to drop. How science has confirmed the benefits of these herbs in their use with low platelets. Why your doctor may not know about these natural alternatives and how you can assist him in helping you. Different tests that naturopathic doctors do to determine your real state of health that may reverse the course of your body drastically. Understand some of the reasons why people develop low platelets. Discover how your digestive tract may be the culprit to your low platelet level problems. How you can prevent the most drastic step a splenectomy. How you can restore your health so that you dont need any more dangerous drugs. Get your life back and stop ending up in the hospital all the time. Learn why your immune system is attacking your platelets and how to calm it down. Learn what over the counter medications to stay away from if you have low platelets Read more here...

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TABLE 2106 Drugs Associated with Thrombocytopenia

LABORAIORY INVESIIGAIION Ihe basic laboratory parameters that should be obtained in a patient with a suspected bleeding disorder are a complete blood count and platelet count, prothrombin time, and activated partial thromboplastin time. Ihe results of these tests coupled with clinical evaluation should enable one to formulate a differential diagnosis. Further hematologic evaluation, using the tables provided in the chapter, can then follow. Hematologic consulation should be sought if the differential diagnosis or the laboratory approach is unclear.

TABLE 2111 Pathophysiologic Mechanisms of Acquired Thrombocytopenia

Acquired qualitative platelet abnormalities, characterized by abnormal platelet function, occur in many disease states ( I.a,b. .e 2.1 1. 2). When present, functional abnormalities can be associated with excessive bleeding regardless of the platelet count. Ta b .e ,.2.1,1 3 outlines some commonly used drugs that can cause platelet dysfunction.

Druginduced immune thrombocytopenia

Some individuals produce antibodies against a drug or drug metabolite that can result in immune platelet destruction. The drugs implicated include quinidine and quinine (stereoisomers of each other), sulfonamides and structurally similar drugs, digitoxin, rifampicin, heroin, morphine, a-methyldopa, gold salts, histamine-2 (H2) receptor antagonists (ci-metidine, ranitidine) and valproic acid. Either the drug or its metabolite, as a hapten, may bind non-covalently to platelet surface proteins and form complete antigenic structures. The susceptible patient produces antibodies that combine specifically with the platelet protein-bound haptenic drug or metabolite. Complement component CI is fixed and activated if immunoglobulin M (IgM), IgGl, or IgG3 is involved in the immune complex. If the classical complement pathway on platelet surfaces is activated completely via CI, C4, C2, and C3 through to the terminal membrane attack complex (C5-C9), then platelets lyse in the circulation....

Thrombocytopenia

Thrombocytopenia is most often caused either by defective platelet production or excessive platelet destruction. Defective platelet production is a common manifestation of many toxic (e.g. chemotherapy), nutritional (e.g. folate or B1Z deficiencies), or neoplastic disturbances of bone marrow hematopoietic stem cell proliferation and differentiation. Thrombocytopenia that is caused by an increased peripheral destruction of platelets is characterized by a shortened platelet survival (normal survival is about 10 days), increased proliferation of marrow megakaryocytes in an effort to compensate for the decreased platelet lifespan, and an increase in the percentage of large (young) platelets in the circulation (normally there are about 10 ). The process is frequently immune mediated.

Anemia Druginduced Immune Hemolytic

It is common experience that a particular drug may cause hemolysis in one patient, thrombocytopenia in another, neutropenia in yet another, and sometimes combinations of these in the one patient. The drug-induced antibodies responsible for these immune cytopenias are cell specific. We are still at a loss to know why a particular drug binds to a particular cell in a particular patient.

Idiosyncrasy of druginduced cytopenias

As already indicated, the antibody may recognize not only the drug but also a specific cell membrane component. Antibodies from patients with drug-induced thrombocytopenia or neutropenia show restriction, in that they react with variable proportions of normal donor cells exposed to the drug (10-80 in one study). This is not related to HI,A or known cell-specific antigens, and family studies suggest that an unidentified polymorphic membrane determinant may be involved as a cell receptor carrier. Another feature of drug-induced antibodies is their extreme heterogeneity from patient to patient and their individual specificity, reflecting a unique immune response.

PThalassemia Phenotype With Normal pGlobin Gene Sequences

A limited proportion of individuals with the p-thalasse-mia carrier phenotype show completely normal p-globin gene sequences as well as normal LCR sequences. Recently, mutations in the general transcription factor TFIIH coding for a specific helicase have also been shown to be associated with p-thalassemia carrier phenotype besides tricothiodystrophy. Furthermore, depending on the site of mutation, mutations in GATA-1 resulted either in dyserythropoietic anemia and thrombocytopenia or thrombocytopenia and p-thalasse-mia carrier phenotype. The results indicate that the p-thalassemia carrier phenotype may result from mutation in a transcription factor regulating the function of the p-globin gene.

Alloantibodies against platelets

In this serious and, from an immunological point of view, interesting reaction, severe thrombocytopenia develops 5-7 days after a transfusion. The reaction occurs in patients, nearly always women, who have become sensitized to a platelet-specific alloantigen, usually as a result of pregnancies but occasionally by blood transfusion. The reaction is thus due to plate-let-specific antibodies, anti-HPA-la in the great majority of cases, but antibodies against other HPA antigens have also been involved. In this reaction, the patient's platelets, which are of course negative for Rarely thrombocytopenia is induced by platelet-specific antibodies in the donor plasma. In contrast to post-transfusion purpura, thrombocytopenia occurs immediately after the transfusion in these cases.

Some of these problems are addressed by dysmorphology databases

If it were possible to rank features (i.e. decide what are the essential features), according to how frequent they are found in reported cases, then this could be easily incorporated into the database and indeed some have tried to do this. If 100 of cases of TAR syndrome (AR standing for aplasia of the radius and the T for thrombocytopenia), despite having radial aplasia, always had the thumb present, then clearly a diagnosis could not be made if it were absent and the computer could be programmed to insist on this.

Coumarintype products

Thromboplastin time are normally in evidence. It should be emphasised that more than a 70 decrease in the activity of an individual clotting agent may be necessary before a prolongation of these assays is evident. Additional tests can be used to differentiate between other causes of coagulopathies, such as thrombocytopenia or diffuse intravascular coagulation, and those caused by this class of compound. Furthermore, assays are available in certain laboratories to detect and measure concentrations of various anticoagulant rodenticides in blood. In recent times, much attention has focused on assays that measure the prothrombin time in a manner that is uniquely sensitive to proteins invoked by vitamin K absence (PIVKA). In this assay, the accumulated procoagulants of the vitamin K-dependent clotting factors act as substrate analogues delaying thrombin activation. Center et al. (2000) reported that the available methodology is sensitive for feline PIVKA proteins and that the test reflects...

Trials with Multiple Agents

It is common in oncology to treat patients with drug combinations. Often, the dose of one agent is fixed and the goal is to find the MTD of the other agent administered in combination. Sometimes, two or three doses of one of the agents are selected with the goal of finding the MTD of the second agent for each dose of the first agent. For example, Rowinsky et al. (1996) described a trial where five doses of topote-can and two doses of cisplatin were selected for the study. Since topotecan and cisplatin cause similar toxicities such as severe neutropenia and thrombocytopenia it was not possible to distinguish which drug caused toxicity. Ivanova and Wang (2004) suggested conducting a single trial that uses the assumption of toxicity monotonicity in both directions, that is, for each agent toxicity is nondecreasing with dose when the dose of the other agent is fixed. Their nonparametric design for the problem uses the bivariate isotonic estimate of the probability of toxicity and is...

Gynecologic Malignancies

The female reproductive tract cancers account for 13 percent of all cancers in women, following breast, lung, and colon cancer. Symptoms occurring as a result of natural progression of malignancy include bleeding, nausea and vomiting, obstructive uropathy, failure to thrive, and or paraneoplastic syndromes. Treatment with surgery, chemotherapy, and radiation can themselves cause complications. Surgical complications include bowel and urogenital tract injury, thromboembolism, and bleeding. Chemotherapy-related complications include anemia, febrile neutropenia, thrombocytopenia, neuropathy, uropathy, nausea and vomiting, extravasation injury, and stomatitis. Radiation-related complications focus mainly on injury to the gastrointestinal and genitourinary tracts.

Pathophysiology Of Transplant Rejection

Metabolites of azathioprine are incorporated into DNA and RNA strands, inhibiting their synthesis and function. The immunosuppressant action of azathioprine occurs through blocking gene activation of stimulated I-lymphocytes. Azathioprine is prescribed at a dose of 2 mg kg day on a continuous basis as maintenance antirejection therapy. Noncompliance with azathioprine has been associated with a high rejection rate. Deleterious effects of azathioprine include leukopenia, thrombocytopenia, hepatotoxicity, and increased risk of neoplasm.

Symptomatic Management

Whereas in the past, splenectomy was frequently performed for the management of severe thrombocytopenia and or for relief of mechanical compression by the greatly enlarged spleen, by removing the main reservoir for Gaucher cells, splenectomy may induce or aggravate liver and bone involvement. Today, splenectomy is rarely indicated.

Haematological effects of splenectomy and hyposplenism

The spleen normally pools up to a third of the circulating platelets. In the immediate period after a splenectomy, the platelet count rise steeply to levels of 600-1000 X 109 l. This thrombocytosis is usually temporary and fall to a level one-third higher than in normal subjects over the following 1-2 months. Occasional large and bizarre platelets can be seen in blood films.

Introduction Clinical Setting

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) share the morphologic lesion of thrombotic microangiopathy (TMA), characterized by platelet thrombi occluding the microvascula-ture. The HUS and TTP syndromes overlap clinically (1-9). Recent evidence indicates differing pathogenesis (see below) TTP is more common in adults, and is characterized by fever, bleeding, hemolytic anemia, renal failure, and neurologic impairment. Hemolytic uremic syndrome is characterized by acute renal failure, nonimmune hemolytic anemia, and throm-bocytopenia, and it is most common in infants and small children. The renal manifestations at presentation include hematuria and low-grade pro-teinuria with elevated creatinine in severe cases. Intravascular hemolysis is evident by increased bilirubin and lactate dehydrogenase (LDH), reticu-locytosis, and low haptoglobin. Both HUS and TTP cause thrombocytopenia, but in our experience, and that of others, this may not be detected by the...

TABLE 1422 Characteristics of Malaria Causing Plasmodium Species

In addition to prolonged high fever, hemolysis, and, in the case of infection with P. falciparum, obstruction to capillary flow, immunologic sequelae may also occur, resulting in glomerulonephritis, nephrotic syndrome, thrombocytopenia, and polyclonal antibody stimulation. Lastly, hypersplenism with resultant pancytopenia may occur, especially in cases of prolonged, untreated malaria.

Clinical Features

The incubation period is short, usually less than 3 days. The most common presenting complaints in early gas gangrene are pain out of proportion to physical findings, as well as a sensation of heaviness of the affected part. On examination, the area may demonstrate a brawny edema with crepitance. The skin will develop a bronze or brownish discoloration with a malodorous serosanguineous discharge, and bullae may be present. Systemic manifestations include a low-grade fever with tachycardia out of proportion to the fever. The patient may be confused or irritable and have a rapid deterioration of the sensorium. Laboratory evaluation may reveal any or all of the following metabolic acidosis, leukocytosis, anemia, thrombocytopenia, coagulopathy, myoglobinemia and myoglobinuria, and liver or kidney disfunction. Gram stain of the bullae often shows pleomorphic gram-positive bacilli with or without spores, red blood cells, but very few white blood cells. Radiologic studies may demonstrate gas...

Hemolyticuremic Syndrome Postdiarrheal

Hemolytic-uremic syndrome presents as acute onset of microangiopathic hemolytic anemia, renal injury, and low platelet count. Most cases occur within 3 weeks of an acute diarrheal illness. A low platelet count is typical early in the illness (within the first 7 days) but may have normalized by the time the patient seeks care. If the platelet count is not less than 150,000 pL within 7 days of the onset of the gastrointestinal illness, consider another diagnosis. Thrombotic thrombocytopenic purpura has similar features and is distinguished from hemolytic-uremic syndrome by the presence of fever and CNS involvement. Additionally, it may have a more gradual onset. Few cases of thrombotic thrombocytopenic purpura are associated with a diarrheal illness.

Table 113 Diagnostic criteria for toxic shock syndrome

Gastrointestinal vomiting, profuse diarrhea Muscular myalgia, or > 5-fold increase in CPK Mucous membrane hyperemia vagina, conjunctiva, or pharynx Renal insufficiency at lease twice normal BUN or creatinine Hepatic at least twice normal bilirubin, transaminases Blood thrombocytopenia (< 100,000 platelett mm3) Central nervous system disorientation without focal neurologic signs Negative serologic results for Rocky Mountain spotted fever, leptospirosis, and measles

H 12421 Medical History

An important part of the medical history is found in the operation note. It describes technical difficulties, iatrogenic vascular injuries, and other problems. Information about preoperative bleeding, substitution, and systemic anticoagulation is found in anesthesia notes. A history of a previous tendency to bleed (for instance, difficulties stopping bleeding after minor wounds, a tendency to bruise easily, or bleeding during tooth brushing) and bleeding complications in previous surgery can be revealed if the patient is awake. Information about current medication with aspirin or clopidogrel is important, along with the most recent INR and ACT values and platelet count.

Bleeding After Aortic Surgery

Substantial hemorrhage during the primary operation can cause a deficiency in coagulation factors. Before starting the reoperation, it is recommended to check if the patient has received packed cells. If the amount administered exceeded four to six units, at least two units of fresh frozen plasma should be given right away. If more than eight units of red blood cells had been given, a thrombocytopenia may contribute to the bleeding.

Medical Treatment and Observation Only

Minor bleeding from surgical wounds and small hematomas is observed with applied compression over the area. For prolonged minor bleeding, hemoglobin, INR and ACT values, and platelet count are checked, and medications affecting the coagulation system are discontinued. These blood samples have a low sensitivity as a screening test for hemostasic function and only 30 of normal co agulation activity is required to obtain normal values. A better measure of platelet function is the number of platelets or the bleeding time. A prolonged bleeding time supports the use of des-mopressin. If a disturbed hemostasis without obvious causes is found, consultation with a coagulation specialist is recommended. A platelet count < 50 x109 l is considered insufficient for hemosta-sis and is an indication for platelet transfusion in case of bleeding. At reoperations platelets should be administered immediately before the start of the operation to give the best possible effect.

Other Considerations for Small Populations

Compared with normal analysis, there is an increased importance to ensure that no false-positive events be present when analyzing rare events. In our study of NKT cells in patients with autoimmune thrombocytopenia, for example, less than 50 positive events could be counted in the samples we had available (9). Clearly then, nonspecific events can skew the data and so results that already have a CV of 20 would become less reliable. As the number of total events acquired increases, so may the number of unspecific events. Again, if a few false-positives were present in a population of 1000 positive events, this may not affect the results very much. But what if only 25 positive events were recorded using the specific antibody and 10 events appeared in the gate when the same high number of total events were acquired and those 10 events were either unlabeled or labeled with a well-chosen isotype control (that is, with the same protein fluorochrome ratio and protein concentration and...

Bone Marrow Transplant

There is a recognized significant risk of morbidity and mortality from neurologic complications following bone marrow transplant (BMT). Subdural hematoma has been reported to occur in up to 12 of patients (all ages), with 75 diagnosed at autopsy without antemortem clinical symptoms.139 Although more commonly occurring in adult BMT patients, SDH has been reported in children as young as 4 years.140 They usually are unilateral in nature, randomly distributed, and variable in size.141 Although the mechanism underlying the cause of the SDH remains unknown, there is an association with pretransplant thrombocytopenia and or coagulopathy.

Other Tropical Diseases

American trypanosomiasis (Chagas' disease), a zoonotic disease caused by T. cruzi, is a public health problem in rural areas of Central and South America.43 Involvement of the CNS is secondary to cerebral embolization of cardiac blood clots.44 Immunologic reactions probably underlie the pathological characteristics of the disease including anaemia, thrombocytopenia, glomerulonephritis, pancarditis and a late-evolving diffuse meningoencephalitis with edema and arachnoiditis. These may cause late-onset epilepsy, with a high frequency of partial seizures.6

Postoperative Care and Complications

Postsplenectomy syndrome causing neutrophil-based leukocytosis and thrombocytosis is not uncommon. Generally no specific therapy is required however, if the platelet count exceeds one million mm3, then antiplatelet therapy should be initiated. The leukocytosis and thrombocytosis are usually self-limited and do not pose a long-term problem.8

Immunocompromised Patients and Health CareAssociated Endocarditis Epidemiology

The increase in nosocomial bacteremia and the related burden of nosocomial endocarditis in newborns is also reflected by the data presented by Opie et al. 46 . In this publication, the incidence of bacterial endocarditis in a level III neonatal nursery was 0.07 . As expected in such young babies the presenting symptoms and signs were often vague and nonspecific. Gestation less than 32 weeks, birth weight less than 1,500 g, thrombocytopenia and neutrope-nia or neutrophilia were common features. The tricuspid valve was involved in seven infants. Of the eight babies six (all of them with tricuspidal

Haematological Disease Anaemia

A full blood count also provides the platelet count (raised in acute blood loss and acute inflammation) and the white cell count (raised in infection). A differential white cell count distinguishes between neutrophilia (bacterial infection, inflammation) and lymphocytosis (viral infection). If the platelet count, white cell count and haemoglobin are all low, this indicates marrow aplasia or infiltration. Abnormalities which may be detected on examination of the blood film include a raised reticulocyte count (haemolytic anaemia, continued bleeding), sickle cells or malarial parasites. Further investigation may be indicated before blood transfusion, e.g. additional blood tests (ferritin, vitamin B12, folate, reticulocyte count, direct Coomb's test) or bone marrow aspiration.

Complications after splenectomy and asplenism

There is an immediate and progressive rise in the platelet count after splenectomy to levels of 600-1000 X 109 l. After a peak at days 7-12, platelet levels usually return to normal, but it may remain elevated for up to 3 months. If the platelet count is persistently elevated above 1000 X 109 l, prophylaxis against deep vein thrombosis should be instituted for example, oral aspirin at 150 mg day.

Coagulation and Hematologic Disorders

Hemophilia, afibrinogenemia, leukemia, and thrombocytopenia (various types) have all been reported to cause SDH in school-age children. Although minor trauma has been put forward as a common cause, SDH may be spontaneous in nature.51,52 Four-factor deficiency is a very rare, autosomal recessive, inherited bleeding disorder involving the vitamin K-dependent coagulation factors. A single case of a 3-month-old male child with the deficiency who presented with a right-sided SDH has been reported.53

Systemic lupus erythematosus

SLE is considered to be a rare, multisystemic, autoimmune disorder that most frequently involves the musculoskeletal, haematopoietic, cutaneous and urinary systems. Cutaneous manifestations of feline SLE are exceptionally rare and may include generalised alopecia, scaling and crusting, involving the face, pinnae, neck, ventrum and limbs, and crusting of all digital pads. The histological features may include interface dermatitis, interface folliculitis, epidermal basal cell and follicular basal cell vacuolation with necrosis. The immunological basis for the latter changes is thought to involve keratinocyte apoptosis mediated by T-lymphocytes that infiltrate the epidermis evidence for this process is lacking in the cat. In addition, there is often immunohistochemical evidence of immune complex deposition at the basement membrane zone. Glucocorticoid therapy with 4 mg kg per day for 1 month initially was effective in establishing control of one case with a positive ANA titre, oral...

Platelet Abnormalities

Acquired platelet abnormalities include both quantitative and qualitative defects. Quantitative problems are usually associated with bleeding complications at a platelet level of less than 50,000 pL with spontaneous bleeding, including central nervous system (CNS) hemorrhage, likely at a level below 10,000 pL. Ta.ble ,.2,ll.-1 depicts the causes of acquired thrombocytopenia I .ble 210-6 displays the drugs most commonly associated with thrombocytopenia. Platelet counts above 400,000 pL are encountered most commonly in inflammatory reactions, patients with malignancy, splenectomized patients, and those with polycythemia vera. Thrombocytosis can be associated with bleeding or thrombosis and is considered an emergency when platelet levels exceed 1 million pL or are associated with evidence of CNS dysfunction or acute thrombosis or hemorrhage.

TABLE 2113 Commonly Used Drugs Associated with Platelet Dysfunction

The emergency management of patients with thrombocytopenia is based on the control of acute hemorrhage and maintenance of an adequate intravascular volume to maintain normal hemodynamics. Most patients with active bleeding and platelet counts less than 50,000 pL should receive platelet transfusion. Each unit of platelets infused should raise the platelet count by 10,000 pL. Patients with platelet antibodies, such as those with idiopathic thrombocytopenic purpura (ITP) or hypersplenism, are unlikely to respond to platelet transfusions. Some disease states, such as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP), actually may be exacerbated by platelet transfusion hematologic consultation should be obtained. All patients with platelet counts less than 10,000 pL should receive immediate platelet transfusion, regardless of the underlying etiology, because of the high risk of spontaneous hemorrhage. Nonemergency therapies for thrombocytopenia with...

Infection With Human Immunodeficiency Virus

The current use of combination therapy, including the use of protease inhibitors, for the treatment of HIV-1 infection has improved the morbidity and mortality associated with HIV-1 infection significantly. These therapies, however, have not yet had a significant impact on the hemostatic abnormalities commonly seen in patients infected with HIV-1. The most common hemostatic abnormalities observed in patients infected with HIV-1 are thrombocytopenia and acquired circulating anticoagulants lupus-type anticoagulants and anticardiolipin antibodies. Thrombocytopenia is one of the earliest findings in asymptomatic HIV-1-infected individuals. Three to 60 percent of all HIV-1-infected patients will have thrombocytopenia at some time during the course of their illness. Both increased peripheral platelet destruction and decreased platelet production occur. Patients infected with HIV-1 have an increased incidence of immune platelet destruction, such as ITP. HIV-1 also can directly infect bone...

Immunopharmacological activities of lipophilic MDP derivatives

The lipophilic derivatives show enhanced interaction with macrophages and improved pharmacokinetics, and thus exhibit higher biological activities than MDP. Four such derivatives, MDP-l.ys(Ll 8) (romurtide), B30-MDP, MTP-PE and murabutide. have been studied extensively for their immunopotentiating effects and toxicity. Romurtide is effective against experimental infections not only when injected before challenge (immunoprophvlaxis), but also when injected simultaneously with or after challenge (immunotherapy). One of the underlying mechanisms of the stimulating effect of romurtide on host resistance is an extremely strong hematopoietic activity for granulocytes and monocytes. Romurtide became the first clinically licensed MDP derivative employed to induce bone marrow recovery following radiation therapy in cancer patients. In patients treated with romurtide, the duration of granulocytopenia is shortened and the number of episodes of infection reduced, allowing completion of cancer...

Parenteral Anticoagulants

The two major complications of unfractioned heparin are major bleeding episodes and heparin-induced thrombocytopenia. Bleeding is related to the degree of anticoagulation and can be prevented by laboratory monitoring with dose adjustment. In the event of major hemorrhage, the infusion can be stopped, and the anticoagulant effect will be greatly diminished in a few hours. Heparin-induced thrombocytopenia (HIT) is due to an antibody, usually IgG, that attaches to and stimulates platelets. This platelet activation produces both thrombocytopenia and a tendency for thrombosis. The incidence of HIT is between 1 and 3 percent in patients treated with unfractionated heparin but significantly less in patients treated with LMW products. The onset of HIT is usually 5 to 12 days after heparin treatment is started but may be sooner for patients who developed the antibody from a previous exposure. The platelet count nadir is often modest, typically 20,000 to 150,000 per pL. Thrombosis may involve...

Further Reading

Cherry KJ Jr, Roland CF, Pairolero PC, et al. Infected femorodistal bypass is graft removal mandatory J Vasc Surg 1992 15(2) 295-303 Drews RE. Critical issues in hematology anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. Clin Chest Med 2003 24(4) 607-622 de Figueiredo LF, Coselli JS. Individual strategies of hemostasis for thoracic aortic surgery. J Card Surg 1997 12(2 Suppl) 222-228 Fujitani RM. Revision of the failing vein graft outcome of secondary operations. Semin Vasc Surg 1993 6(2) 118-129

Hematologic Syndromes

The association of bleeding diathesis and intravascular coagulopathy abnormalities in patients with prostate cancer has been reported. Bleeding problems in the prostate cancer patient may result from the effects of the tumor on hemostatic mechanisms or from the treatment of the tumor by cytotoxic and other agents. Among the tumor-related bleeding problems are disseminated intravascular coagulation, primary fibrinolysis, thrombocytopenia, acquired platelet dysfunction, and circulating inhibitors or anticoagulants. Disseminated intravascular coagulation is associated with hypercoagulability state in most solid tumors, whereas in prostate cancer tumors the most common presentation is acute promyelocytic leukemia bleeding. Treatment-related bleeding disorders include the common problem of thrombocytopenia secondary to myelosup-pressive chemotherapy as well as the interesting micro-angiopathic hemolytic anemia syndrome associated with mitomycin C and other agents (de la Fouchardiere et al....

Severe preeclampsia

Delivery should be initiated, after a course of antenatal corticosteroid therapy if possible, when there is poorly controlled, severe hypertension, eclampsia, thrombocytopenia (less than 100,000 platelets microL), elevated liver function tests with epigastric or right upper quadrant pain, pulmonary edema, rise in serum creatinine concentration by 1 mg dL over baseline, placental abruption, or persistent severe headache or visual changes. Fetal indications for delivery include nonreassuring fetal testing, severe oligohydramnios, or severe fetal growth restriction (less than the 5th percentile).

Pathologic Findings

Although more prevalent with higher doses of CsA in the 1980s, thrombotic microangiopathy (Fig. 21.3) still occurs under current regimens, even with careful attention to blood CsA levels. By 1994, the prevalence of CsA-associated thrombotic microangiopathy had decreased to 0.9 , accounting for 26 of the cases of thrombotic microangiopathy after renal transplantation (acute rejection, probably humoral, accounted for 53 and recurrent thrombotic microangiopathy 16 ) (5). Patients typically present with acute renal failure, thrombocytopenia, microangiopathic hemolytic anemia, elevated lactic dehydrogenase, and hyperbilirubinemia. Despite these characteristic features, the clinical syndrome is not often recognized before biopsy. Those without systemic signs (thrombocytopenia, hemoly-sis) do considerably better (6).

Ticlopidine and clopidogrel

Ticlopidine has proven its usefullness in conjunction with aspirin in the prevention of acute and subacute stent thrombosis. This complication occurs after insertion of an intra-coronary stent in 2-8 of cases, usually between days 2 and 14 with a peak between days 5 and 7 after stent placement. Very extensive regimens, consisting of vitamin K antagonists, dipyridamole, and dextran as well as aspirin and heparin, did not positively influence this complication and led to unacceptable bleeding complications.16 However, the combination of aspirin and ticlopidine achieved a significant decrease of stent thrombosis as well as bleeding complica-tions.35 Simultaneously, significant improvement of stent delivery technique such as high pressure implantation also affected results. Until recently, the standard of practice was to administer ticlopidine daily, beginning 7 days before scheduled stent placement. If a stent is inserted as a bailout procedure or because of a suboptimal result, it is...

Molecular Diversity Of

Type 2B VWD is characterized by increased affinity of the mutant VWF for platelet and reduction in high molecular weight multimers (Fig. 2). The remaining VWF multimers are not hemostatically effective and cause bleeding and thrombocytopenia in the patients that can be exacerbated during physical exercise, stress, and pregnancy. This defect is identified in the laboratory by enhanced ristocetin-induced platelet aggregation. Type 2B is inherited as an autosomal dominant and accounts for less than 20 of all type 2 VWD. Aside from a single amino acid insertion, the genetic defect is generally found to be a point mutation in the A1 domain of VWF gene that contains the glycoprotein Ib (GpIb) binding domain and results in a gain of function. The most frequent mutations are Arg1306Trp, Arg1308Trp, Val1316Met, and Arg1314Gln accounting for 90 of the subtype.

Epsteinbarr Virus Infectious Mononucleosis

Hematologic complications include autoimmune hemolytic anemia and thrombocytopenia. Corticosteroids will benefit some patients with hematologic complications and should be initiated in the emergency department for those admitted with severe anemia or severe thrombocytopenia. Refractory severe thrombocytopenia may be treated with splenectomy.

Cirrhosis and Complications of End Stage Liver Disease

Emergency Medacine For Liver Disease

Hemorrhage is heralded by hematemesis, hematochezia, and or melena, plus varying degrees of hemodynamic instability. Complicating factors include preexisting anemia, thrombocytopenia, and coagulopathy. The differential diagnosis of acute gastrointestinal hemorrhage in the cirrhotic is less important than identification of a condition that requires aggressive managment and appropriate consultation. Basic priorities in management include airway protection and appropriate intravenous access for the infusion of fluids and blood products. Significant coagulopathy should be assumed, and placement of central venous catheters should be performed with extreme caution. Gastric lavage is indicated when active bleeding is suspected to evacuate the stomach and help alleviate repeated vomiting, which can exacerbate hemorrhage. Gastric lavage provides some indication of the location of hemorrhage and a gross assessment of ongoing blood loss. The presence of known gastroesophageal varices is not a...

Deep Venous Thrombosis or Pulmonary Embolism

Treatment for acute DVT or PE can be accomplished with unfractionated heparin using a weight-based intravenous regimen with monitoring by the aPTT and subsequent adjustments guided by the results. Alternatively, acute PE or DVT can be treated with LMW heparin, either enoxaparin 1 mg kg or dalteparin 100 IU kg, administered subcutaneously twice a day. The advantages of LMW heparin are a more predictable anticoagulant effect, easier administration, no requirement for laboratory monitoring, and a decreased risk of complications (major bleeding and heparin-induced thrombocytopenia). LMW heparin appears to be as effective as unfractionated heparin in the treatment of acute DVT or PE and, with the abovementioned advantages, has much to recommend it. The major disincentive to using LMW heparin is greater cost than for unfractionated heparin.

Therapeutic use of IFNa

Effects, including fever, headache, chills, fatigue, anorexia, leukopenia and thrombocytopenia. Despite their current limitations, IFNs are now well established as useful drugs. IFNa is the most widely used and has received approval in many countries, including Food and Drug Administration (FDA) approval in the US, for several clinical indications. Since 1986 it has been used as a therapy against haii v-cell leukemia. Significant regression of the cancer is observed in more than 90 of patients. Since 1988, IFNa has been successfully used as a therapy against diseases associated with human papillomavirus infection such as juvenile laryngeal papillomatosis and condyloma acuminatum. Since that same year it has also been used in the treatment of Kaposi's sarcoma in patients infected with HIV. Around 30 of the patients who reccive IFNa, however, withdraw from treatment because of side-effects associated with the high IFNa doses. In 1991, IFNa was licensed for the treatment of chronic...

TABLE 2114 Hemostatic Abnormalities in Patients with Liver Disease

Thrombocytopenia This is most often due to portal hypertension, which leads to hypersplenism and splenic sequestration. Ethanol causes direct bone marrow suppression and reduced production of all hematopoietic cells including platelets. Patients with mild or moderate hepatic dysfunction most often have subclinical hemostatic abnormalities. Those with severe liver disease may have life-threatening bleeding. Laboratory studies that should be obtained include hemoglobin hematocrit, PT, aPTT, thrombin clotting time (TCT), and platelet count. Fibrinogen levels and measurement of FDPs or D-dimers may not be readily available. In general, prolongation of the PT is a poor prognostic sign in patients with liver disease.

Diseases caused by maternal antibodies

Thrombocytopenia and neutropenia in the newborn child can also occur due to maternal isoantibodies, but these disorders are much rarer than hemolytic disease. The disease is relatively common in women of child-bearing age and characterized by thrombocytopenia caused by autoantibodies, usually of the IgG isotype. The antibodies bind to circulating thrombocytes that are either lysed or are destroyed by phagocytosis. The level of platelet-bound IgG correlates well with severity of the disease. The condition was early recognized as a cause of neonatal thrombocytopenia. The maternal levels of thrombocytes and platelet-bound antibodies do not correlate well with the fetal platelet count which makes blood sampling from the fetus necessary to predict the outcome. The incidence of the neonatal disease is 60 , with a mortality of about 15 , principally due to intracranial hemorrhage. Neonatal thrombocytopenia also occurs in mothers cured by splenectomy, since the relevant antibodies are still...

Hematologic Disorders Affecting the Spleen Hereditary Spherocytosis

Platelet counts generally tend to be less than 50,000 mm3 and can even be undetectable. The hallmark of ITP is ecchymosis and purpura with bleeding. Bleeding can present as benign spontaneous epistaxis or gingival bleeding as well as significant potentially life-threatening gastrointestinal hemorrhage or hematuria. Therapy for ITP consists of corticosteroids for a period of 4-8 weeks. In those with refractory disease, immune globulin infusions and plasmapheresis may also be warranted. Splenectomy is reserved for patients that do not respond with an elevation of their platelet count to more than 75,000 mm3 following medical therapy. Additionally, splenectomy may also be performed in patients that develop recurrent disease with reduction of corticosteroids. Medical therapy has approximately a 20 percent permanent cure rate, while surgery approaches approximately 85 percent. Patients who develop recurrent disease after splenectomy require evaluation for accessory spleens by technetium...

Complications of chemotherapy

Most cytotoxic drugs can cause bone-marrow toxicity (myelosuppression). Vincristine is generally regarded as minimally myelosuppressive in dogs, but has been reported to cause significant myelosuppression in cats (Hahn el ah, 1996). Neutropenia is one of the more common complications of chemotherapy and is the major dose-limiting factor. Neutrophil counts < 2 X 109 1 can be life threatening, with a risk of overwhelming sepsis. Thrombocytopenia can occur, but is rarely severe enough to cause bleeding. Mild anaemia may also occur, but is often indistinguishable from anaemia of chronic disease. It is essential that a blood sample is taken for full haematology as a baseline before embarking on a course of chemotherapy and regular monitoring will be required to assess for myelosuppression throughout treatment (at least every 3 4 weeks, or more frequently depending on the protocol used).

Thiazides and Loop Diuretics

The toxicity associated with thiazides and loop diuretics involves two basic processes volume contraction and electrolyte derangements. Symptoms associated with intravascular volume depletion include hypotension, tachycardia, and altered mental status. Common electrolyte derangements include hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia, and hypochloremic metabolic alkalosis. Other adverse reactions from thiazides and loop diuretics may include rash, pruritis, hearing loss, leukopenia, and thrombocytopenia.

Laboratory Evaluation

Further laboratory testing and imaging studies should be undertaken next, directed by which type of jaundice is present. If the initial laboratory studies suggest hepatocellular disease and the clinical examination suggests viral hepatitis, then serologic studies for viral hepatitis should be done. If the clinical picture points to alcoholic liver disease or other toxins, then prothrombin time, platelet count, and serum albumin levels should be determined to help estimate the degree of liver injury. If results of the serologic studies are negative, there is no improvement with withdrawal of the suspected toxic agent, or there is no other obvious etiology, liver biopsy should be considered.2

Potential clinical significance of IL11

Domized phase II trial in cancer patients who had previously received platelet transfusions for severe chemotherapy-induced thrombocytopenia. Ninety three patients who had received platelet transfusion for nadir platelet counts less than 20 000 pi during chemotherapy cycle immediately prior to entry into the study were randomized to receive placebo or IL 11 at doses of 25 or 50 p,g kg subcutaneouslv once daily for 14 to 21 days beginning one day after chemotherapy. Chemotherapy was continued during the study without dose reduction. The results demonstrated that IL-11 treatment at a dose of 50 pg kg significantly reduces the need for platelet transfusion in subsequent chemotherapy cycles for patients who had required platelet transfusions for severe thrombocytopenia in a previous cycle. The thrombopoietic effect of IL-11 is being further evaluated in other phase II and phase III trials.

Use of Diuretics in the Treatment of Hypertension in Pregnancy

Hypertension in pregnancy can be broadly divided into preexisting hypertension (chronic hypertension), hypertension of pregnancy (usually appearing within the first trimester, but can develop at any time) and preeclampsia eclampsia (occurring in the third trimester). Preeclampsia is characterized by hypertension, proteinuria, edema, and hyperuricemia, with or without associated liver dysfunction and coagulopathy (HELLP syndrome hemolysis, elevated liver enzymes, and low platelets). Eclampsia is diagnosed when hypertension is severe and convulsions occur. An early indication of developing hypertension in pregnancy is failure to observe the normal fall in BP during the

Gender Differences In Pd And Clinical Endpoints

In the article by Mougenot et al. (188) that was cited in the previous section, population modeling was applied to evaluate covariate effects on PK parameters of melphalan infused over a 24-hour period in patients with advanced malignancies. Highly significant and pronounced gender effect on CL was identified. In an attempt to establish an exposure-response relationship, the authors plotted the percentage decreases in red blood cells count, white blood cells count, and platelet count at the nadir during each chemotherapy course against AUC. As one could expect from such a simplistic analysis, no relationship was found. It seems the adequate mechanistic-based PK-PD analysis would use indirect-response models (239), in particular, models that take into account the cell turnover and cell life-span (240-244). The PK-PD modeling approach would enable researchers to explore the impact of patient covariates like gender on essential processes involved, including the drug effect.

Acquired Immunodeficiency Syndrome

There are numerous oral manifestations of HIV infection. Primary HIV infection, occurring from 1 to 6 weeks after contact, is an acute viral syndrome but may have associated intraoral findings such as a sore throat, mucosal erythema, and focal ulceration. Persistent generalized lymphadenopathy, particularly of the cervical lymph nodes, is present in 70 percent of otherwise asymptomatic HIV-infected patients. The presentation of acquired immunodeficiency syndrome (AIDS) is highly variable, and numerous oral manifestations can occur. Oropharyngeal candidiasis is the most common oral finding and may lead to the initial diagnosis of AIDS. HIV-related gingivitis is distinctive, presenting as a 2- to 3-mm linear band of erythema along the gingival free margin. Periodontitis among the HIV-infected population is common and usually more aggressive and painful in its presentation. Such necrotizing periodontitis is distinguished from acute necrotizing ulcerative gingivitis, which is also a...

New onset proteinuria hypertension and at least one of the following

Thrombocytopenia Less than 100,000 platelets per mm3 2. Laboratory evaluation consists of hematocrit (hemoconcentration suggests preeclampsia), platelet count, protein excretion, serum creatinine, serum uric acid, serum alanine and aspartate aminotransferase concentrations (ALT, AST), and lactic acid dehydrogenase concentration (LDH). G. Hematologic changes. Increased platelet turnover is a consistent feature of preeclampsia. The most common coagulation abnormality in preeclampsia is thrombocytopenia.

Rocky Mountain Spotted Fever

Laboratory diagnostic confirmation is difficult during the early phase of the disease, frequently mandating treatment based on clinical criteria. Serologic tests are used to confirm the diagnosis of RMSF. Some laboratory data may be helpful in establishing the presumptive diagnosis early, such as hyponatremia, leukopenia, and thrombocytopenia.

Indications for Hospital Admission

Infants and children with bloody diarrhea may have a gastrointestinal infection due to Escherichia coli O157 H7 and are at risk of developing HUS. The source most frequently identified in outbreaks has been exposure to undercooked ground meat, undercooked poultry, eggs, or unpasteurized milk. Person-to-person transmission, especially in child day-care centers, is also a well-recognized risk factor for childhood HUS. The risk is highest for children under 5 years of age who are infected with E. coli O157 H7 and may approach 13 percent.6 Any child who presents with acute bloody diarrhea and laboratory evidence of hemolytic anemia, thrombocytopenia, and or elevated serum creatinine should be admitted.

TABLE 2204 Criteria for Intravenous Thrombolysis in Ischemic Stroke

DOSING, ADMISSION, AND COMPLICATIONS The total dose of rt-PA is 0.9 mg kg, with a maximum dose of 90 mg 10 percent of the dose is administered as a bolus, with the remaining amount infused over 60 min. Blood pressure and neurologic checks should be assessed every 15 min for 2 h after starting the infusion. Table 220-5 outlines the emergent management of hypertension following thrombolytic administration. No aspirin or heparin is given in the initial 24 h following treatment. Patients should be admitted to an ICU setting familiar with the use of thrombolytic drugs and neurologic monitoring. Intracerebral bleeding should be suspected as the cause of any neurologic worsening until repeat CT imaging is obtained. If bleeding is suspected, a CBC with platelet count, coagulation studies, fibrinogen and type and crossmatch for 4 units (U) packed red blood cells, 4 U cryoprecipitate or fresh-frozen plasma, and 1 U single-donor platelets should be obtained. An emergent hematology and...

Biological activities of IL11

IL-11 is a bone marrow fibroblast-derived cytokine with a variety of in vitro biological activities within the hematopoietic, lymphopoietic, hepatic, adipose, bone and neuronal systems. IL-1 I has been tested in various animal models including mice, rats, hamsters, rabbits and nonhuman primates. Some of these in vitro and in vivo studies are summarized in Tables 2-4. It appears that IL-11 may be a potential therapeutic agent for thrombocytopenia and neutropenia following myeloablative therapy and bone marrow transplantation.

Platelet antigenicity

GPIb is a target on the platelet surface for the attachment of quinine quinidine drug-dependent antibodies. The result of this drug-antibody binding to (or near) platelet GPIb molecules is usually severe thrombocytopenia. Some patients with 'idiopathic' autoimmune thrombocytopenic purpura (ITP) make autoantibodies that are directed against antigenic components of either GPIb or, more commonly, the GPIIb-IIa complex. The platelet-specific alloantigens Leka and P1A1 are located on GPIIb and Ilia, respectively. Following transplacental isoimmunization, anti-PlAi or anti-Lek'1 can cause neonatal thrombocytopenia. PlAI-specific antibodies reactive with the P1AI antigenic locus on GPHIa have also been implicated in the still enigmatic pathogenesis of post-transfusion purpura. It is perhaps important that GPIIIa molecules have been found on endothelial cell membranes and might also be a target of PlA1-specific antibodies (with resultant endothelial cell damage) in patients with this rare...

Patient Selection And Technique

The evaluation of patients with ascitic fluid collections should be as rigorous for laparoscopic procedures as those performed for major surgical resections. As stated above, general anesthesia is frequently required because of the need for performance of pneumoperitoneum, abdominal relaxation and length of intraabdominal examination required to avoid missing small occult lesions. Assessment of cardiac and pulmonary function is important to avoid post-procedure complications. Radiographic evaluation of the chest is mandatory to determine whether pleural effusion is present along with abdominal fluid collections. Diagnostic or therapeutic thoracentesis should be performed when necessary with full radiologic evaluation afterward to insure that pneumothorax has not resulted. Pre-laparoscopic determination of coagulation abnormalities, especially in patients with underlying hepatic disease is important. Assessment of prothrombin time and partial thromboplastin time as well as platelet...

Complications Of Immunosuppressive Agents

Azathioprine interferes with both B- and T-cell responses to antigenic stimulation. Generalized myelosuppression is a common side effect resulting in leukopenia and, to varying degrees, thrombocytopenia and anemia (megaloblastic) and is generally seen within the first few weeks. Other observed toxicities include hepatitis, cholestasis, hepatic vein thrombosis, pancreatitis, dermatitis, and alopecia. Prolonged use also predisposes to malignancies such as squamous cell carcinoma of the skin and lip, cervical carcinoma, and lymphoproliferative disorder.

Clinical aspects in human medicine

Immune complexes are found in the circulation and or other biological fluids of patients with a large spectrum of diseases not resembling each other, such as autoimmune, infectious and neoplastic disorders. This proves that elimination of antigens in the stage of immune complexes is a common feature to many diseases, and symptoms may nor necessarily result from their presence. In fact, in many circumstances, it is not possible to differentiate between a role for immune complexes in physiological antigen removal and a deleterious pathogenic factor. In glomerulonephritis the pathogenic role of immune complexes is generally accepted. The following immune complex diseases are frequently associated with nephritis SLE, polyarteritis, cryoglobulinemia and many microbial diseases such as bacterial endocarditis, leprosy, malaria, trypanosomiasis, hepatitis B and C infection and dengue hemorrhagic fever. In contrast, RA, polymyositis, dermatomyositis, cutaneous vasculitis, fibrosing alveolitis...

TABLE 1013 Criteria for Hypertension Preeclampsia and Eclampsia

The HELLP syndrome (an acronym for hemolysis, elevated liver enzymes, and low platelets) is an important clinical variant of preeclampsia that has a predilection for the multigravid patient, in contrast to the primigravida, in whom preeclampsia is more common. In the HELLP syndrome, the blood pressure is variable and may not be elevated initially. This fact, combined with the usual complaint of epigastric or right upper quadrant pain, makes it easy to mistake the HELLP syndrome for other causes of abdominal pain, such as gastroenteritis, hepatitis, pancreatitis, or pyelonephritis. The HELLP syndrome should be considered in any pregnant or postpartum patient who presents to the emergency department with a chief complaint of abdominal pain. The diagnosis can be made based on clinical findings coupled with laboratory results (Table 1.0.1.-4).

Necrotizing Enterocolitis

The medical management consists of bowel rest, with the infant receiving nothing by mouth, and gastric decompression with a nasogastric tube. Cultures of blood, urine, and cerebrospinal fluid should be obtained. Ampicillin and cefotaxime 100 mg kg q 8 to 12 h should be administered. The blood pressure and hydration status should be maintained with liberal use of crystalloids and Plasmanate. Fluid intake may have to be increased to 200 (mL kg) 24 h and inotropic agents used if needed. Thrombocytopenia, neutropenia, and disseminated intravascular coagulopathy are often seen in neonates who are deteriorating, and platelet transfusions should be administered if there is evidence of systemic or gastrointestinal bleeding. Respiratory support may be required, and any acidosis should be corrected. Patients with early necrotizing enterocolitis should have close clinical observations and serial x-rays to look for signs of gangrene or intestinal perforation. The medical treatment includes bowel...

Biliary Complications

Liver transplant recipients with suspected biliary complications should be referred to a transplant center. All patients should have a complete blood count (CBC) with platelet count and differential serum chemistries including electrolytes, blood urea nitrogen (BUN), creatinine, liver function tests, amylase, and lipase levels cultures of blood, urine, bile, and ascites if present chest x-ray and abdominal ultrasound with Doppler flow studies. Ultrasound rules out the presence of fluid collections, screens for the presence of thrombosis of the hepatic artery or portal vein, and identifies any dilation of the biliary tree. The intrahepatic ductal system rarely appears dilated appreciably by ultrasound, even in the presence of complete obstruction. Patients often require cholangiography for complete evaluation. Those patients with choledochocholedochostomy are best evaluated by endoscopic retrograde cholangiopancreatography (ERCP) because it permits both a radiographic diagnosis and the...

TABLE 1875 Complications of Heatstroke

Widespread hematologic disorders may be apparent both clinically and on laboratory evaluation. Purpura, conjunctival hemorrhages, petechiae, pulmonary, gastrointestinal, and renal hemorrhages may be present. Coagulation studies may show thrombocytopenia, hypoprothrombinemia, and hypofibrinogenemia. Thermal injury to the vascular endothelium causes increased platelet aggregation, changes in capillary permeability, thermal deactivation of plasma proteins resulting in a decreased level of clotting factors, and, rarely, disseminated intravascular coagulation or fibrinolysis.

Toxic Epidermal Necrolysis

Prolabial blistering and erosive lesions are disfiguring and often impair adequate oral intake, contributing to hypovolemia. Ocular complications include purulent conjunctivitis, painful erosions, and potential blindness. Anogenital lesions are common. Additional mucous membrane involvement includes the gastrointestinal, urinary, and respiratory tracts. The two major complications and leading causes of death in TEN are infection and hypovolemia with electrolyte disorders. A broad range of pathogens is usually found, with staphylococcal and pseudomonal species predominating. The mortality rate has been reported as being between 25 and 30 percent. These clinical variables are associated with poor prognosis advanced age extensive disease idiopathic nature multiple medication use steroid therapy azotemia hyperglycemia leukopenia and thrombocytopenia.7 The differential diagnosis of TEN includes staphylococcal scalded skin syndrome (SSSS) EM, toxic shock syndrome (staphylococcal and...

Therapeutic options for immunemediated skin diseases

Cats that are responding poorly with steroid therapy are potential candidates for chlorambucil therapy daily or every other day, in combination with steroids, using 0.1-0.2 mg kg. Tablet size is 2 mg, so most cats receive half a tablet per day. The mode of action is on DNA synthesis and inhibition of rapidly proliferating cells at all stages of the cell cycle. Therapy has to be given for 4-8 weeks and side-effects may include vomiting, diarrhoea, anorexia and, more importantly, bone-marrow suppression. The initial therapy can be combined with prednisolone at 2 mg kg per day. After initial therapy an alternate-day dose regimen is given for the chlorambucil and prednisolone thereafter, one should be able to stop chlorambucil and use glucocorticoids alone. Cats should be monitored with haematology samples for white cell and platelet counts, every 2 weeks (Helton-Rhodes, 1995). migration, lymphocyte function and immunoglobulin production. It may take 6-12 weeks to see the full response to...

Reactivation Tuberculosis

Miliary tuberculosis is the result of wide hematogenous spread during the primary infection, or secondary seeding of the other organs in an immunocompromised host. Fever, cough, weight loss, hepatomegaly, splenomegaly, lymphadenopathy, and signs of multisystem illness should cause one to suspect miliary disease. Laboratory abnormalities include hyponatremia, anemia, thrombocytopenia, and leukopenia. The chest radiograph shows diffuse nodular infiltrates. 4

Clinical Description

Although some patients are asymptomatic with coincidental detection of a leukocytosis on routine medical evaluation, the chronic phase of disease typically has an insidious onset with symptoms related to hypermetabo-lism, including fatigue, anorexia, weight loss, and night sweats. Massive splenomegaly is common. With disease progression, patients typically develop worsening anemia and thrombocytopenia. Without treatment, the median survival of CML is 4-5 years from diagnosis.

Table 142 Etiology of epistaxis

Local irritants Cocaine, nasal sprays, cigarette smoke, toxic gases Inflammatory Rhinitis, sinusitis, granulomatous disease Mass lesions Nasal sinus tumors, carotid artery aneurysm Medications Anti-platelet agents, NSAID's, warfarin, heparin Systemic disease Liver renal failure, DIC, thrombocytopenia

Thrombolysis in Acute Ischemic Stroke

ROLE OF THE EMERGENCY DEPARTMENT Specific critical pathways similar to those used for AMI (Door, Data, Decision, Drug) should be used to speed the evaluation of patients with acute stroke. Triage personnel should be educated to identify patients with symptoms of acute stroke and instructed to immediately place such patients in a monitored bed and initiate the aforementioned general recommendations. Automatic studies include a CBC with platelet count, coagulation profile, type and screen, bedside glucose determination, and an electrocardiogram. The emergency physician should be notified of a potential acute stroke, and an acute stroke system, if in place, should be activated.

Antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a disorder of recurrent arterial and or venous thrombosis and thrombocytopenia associated with the presence of antiphospholipid antibodies (aPL). Although scattered case reports existed, the term APS was first used in 1985 with tentative criteria being proposed in 1987. Approximately 50 of these patients are considered to have the primary APS (PAPS) and 50 secondary APS (SAPS). SAPS seems to be clinically aPL are a heterogeneous group of antibodies which occur in certain autoimmune diseases, especially SLE, PAPS, syphilis and other infectious diseases, and in normal individuals. Autoimmune aPL include the LA and aCL and, as mentioned above, are associated with thrombosis, recurrent fetal loss and thrombocytopenia. Although aPL are heterogeneous in their specificities, those that react with anionic phospholipids and ( -glycoprotein 1 ( 32GP1) 02GPl-dependent aCL) are associated with the clinical manifestations of APS. In addition to LA and aCL,...

TABLE 2142 Characteristics of Acquired Hemolytic Anemias

The diagnosis of TTP represents a medical emergency. Patients should be treated by experienced hematologists. Rapid transport to a tertiary care center is indicated. Some centers have a policy of initially admitting all TTP patients to an intensive care unit. When the diagnosis of TTP is established or suspected, fresh-frozen plasma should be infused immediately. The foundation of therapy for TTP is plasma exchange transfusion (PLEX). Some patients will respond favorably to plasma infusions alone, and these can be given until the exchanges can be initiated. The plasma exchange uses fresh-frozen plasma (FFP) or fresh unfrozen plasma (FUP). The plasma is thought to provide a substance that the patient is lacking or remove an unknown toxic substance. These exchanges may be required daily for a period of several months. TTP patients are also treated with prednisone (or methylprednisolone), 1 mg kg per day, and antiplatelet therapy consisting of aspirin or dipyridamole. Refractory patients...

Timing and indications for delivery

Delivery should be undertaken if there are signs of worsening disease (eg, severe hypertension not controlled with antihypertensive therapy, cerebral visual symptoms, platelet count < 100,000 cells microL, deterioration in liver or renal function, abdominal pain, severe fetal growth restriction, abruption, nonreassuring fetal testing).

Immunosuppressive agents

Alternatively, they may be intolerant of, or resistant to, glucocorticoids and poor surgical risks for splenectomy. Clinical benefit has been noted in about 50 of patients. A reasonable trial of this type of agent is about 3-4 months, and if no beneficial effect is noted, therapy is discontinued. If clinical benefit occurs, one can maintain the dosage level for a total of 6 months and then taper over several months. During therapy, patients are instructed to maintain a high fluid intake to reduce the incidence of chemical cystitis seen with cyclophosphamide and the need to have weekly blood counts to monitor bone marrow suppression, which can be seen with any of these immunosuppressive drugs. Dosage should be adjusted to maintain the leukocyte count > 2000, granulocyte count > 1000 and platelet count > 50000-100000 mm

Coronary Heart Disease

The effects of different doses of fish oil on thrombosis and bleeding time have been investigated. A dose of 1.8 g EPA day-1 did not result in any prolongation in bleeding time, but 4 g day-1 increased bleeding time and decreased platelet count with no adverse effects. In human studies, there has never been a case of clinical bleeding, even in patients undergoing angioplasty, while the patients were taking fish oil supplements. Clinical investigations indicate that n-3 fatty acids prevent sudden death. A series of intervention trials have clearly shown that the addition of n-3 fatty acids in the form of fish oil (EPA and DHA) decrease the death rate in the secondary prevention of coronary heart disease by preventing ventricular arrhythmias that lead to sudden death.

Ethical And Societal Considerations

Gaucher disease is caused by an enzymatic defect with consequent accumulation of glucocerebroside. Type I, the nonneuronopathic form, is rather common, with a predilection among Ashkenazi Jews. There is tremendous variability in age of onset, severity, and phenotypical expression in this type. Symptomatic presentation may include hepatosplenomegaly, anemia, thrombocytopenia, and skeletal or lung involvement. Life expectancy is unimpaired. The neuronopathic forms are pan-ethnic with a continuum of neurological and visceral signs and symptoms, and with decreased life expectancy. Diagnosis is performed by assay of p-glucocerebrosidase activity, and molecular analysis of mutations may broadly define genotype-phenotype correlations. ERT has proven to be safe and effective in ameliorating disease symptoms and signs however, it involves life-long intravenous therapy, is costly, and is incapable of crossing the blood-brain barrier. Thus, other forms of treatment, including bone marrow...

Anemia And Coagulation Disorders

Patients with hemoglobin of less than 9 g dL can have significant surgical morbidity. A peripheral blood smear may indicate the etiology of the anemia. Macrocytosis or microcytosis suggests significant anemia, target cells are seen in splenic hypofunction, and spherocytes and schistocytes are seen in hemolytic anemias. The usual initial screening coagulation tests include a PT, aPTT, and a platelet count. Qualitative and quantitative defects are seen in platelets in the presence of uremia and liver disease. Platelet aggregation studies and a bleeding time test can identify qualitative defects in platelets. In idiopathic thrombocytopenic purpura, intravenous immune globulin 2 g kg over 2-4 days can be given to increase platelet counts. If the thrombocytopenia is drug induced, the drug should be stopped and the patient allowed to recover prior to operation. If the surgery cannot be delayed, platelet transfusion should be undertaken.

Some Complications During Intensive Care

Frank hemorrhage in the background of normal coagulation parameters and platelet count means that the bleeding is potentially corrected by surgery. Disseminated intravascular coagulation (DIC) is the activation of blood clotting owing to endothelial and or tissue damage from various nontraumatic and traumatic causes (55). There is

The Geriatric Patient

The prevalence and predictive value of abnormal preoperative laboratory tests in elderly patients (abnormal preoperative electrolyte values and thrombocytopenia) is small and has low predictive values. Although more prevalent, abnormal hemoglobin, creatinine, and glucose values were also not predictive of postoperative adverse outcomes. Routine preoperative testing for hemoglobin, creatinine, glucose, and electrolytes on the basis of age only may not be indicated in geriatric patients. Rather, selective laboratory testing is indicated as suggested by history and physical examination, which will determine patient's comorbidities and surgical risk.15

Substrate Reduction Therapy

A pivotal trial of SRT was carried out in 28 adult patients (from four centers Cambridge, UK Amsterdam Prague and Jerusalem) naive to enzyme therapy, with mild to moderate type I Gaucher disease, who were unable or unwilling to receive enzyme treatment. There was significant reduction in spleen and liver, although amelioration of anemia and thrombocytopenia lagged behind. There were side effects, including diarrhea, abdominal pains, weight loss, tremor, and peripheral neuropathy, which were reversible with dose reduction or withdrawal. 15 A low-dose trial showed dose dependency for clinical improvement but no reduction in severity or frequency of side effects. Finally, using SRT as a maintenance regimen (i.e., switching from ERT or in combination with ERT), at 6 months, there were no clinically significant differences among groups.

Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome is a febrile illness characterized by bilateral interstitial pulmonary infiltrates and respiratory compromise resembling adult respiratory distress syndrome. There is typically a prodrome of fever, chills, myalgias, headache, and gastrointestinal distress. Common laboratory findings include one or more of the following hemoconcentration, left shift in white blood cell count, neutrophilic leukocytosis, thrombocytopenia, or circulating immunoblasts.

Special Investigations

Abnormal findings include anemia, thrombocytopenia, coagulopathy, hyponatremia, and raised urea and creatinine. Hypocalcemia may occur in some cases, subsequent to the chelation of ionized calcium by triglycerides liberated by bacterial lipases. Leukocytosis with a white cell count above 15,000 mm3 and a left shift is found in more than 90 of cases. Neutrophilia indicates overwhelming bacterial infection. It is noteworthy that leukocytosis may not be present in immunosuppressed patients (Baskin et al. 1990 Laucks 1994). Anemia maybe present as part of the septic profile. Coagulopathy may be indicated by a raised prothrombin time (PT) and partial thromboplastin time (PTT), and thrombocytopenia. Raised fi-brinogen levels and positive D-dimers may herald the onset of disseminated intravascular coagulation (DIC).

Other Mycotoxins That Can Occur In Food

T-2 toxin was isolated from strain T-2 of F. sporotrichio-ides misidentified as F. tricinctum isolated from corn associated with cow mortalities (33,114). This compound has been the subject of considerable toxicological study (17) because it is easy to isolate and purify. During World War II, there were large-scale poisoning of the rural population in the former Soviet Union caused by the consumption of grains left in the field over winter (estimates range to 1,000,000 victims). The disease was called alimentary toxic aleukia. Samples of extracts made at the time have been shown to contain the trichothecenes T-2 and HT-2 toxin. Shortly after consuming food prepared with contaminated grain, people reported a burning sensation in their mouths, vomiting, weakness, fatigue, and tachycardia. After a period of time, affected individuals felt better, but there was a progressive leucopenia, anemia, and decreased platelet count, lowering the resistance of the body to bacterial infection. As...

TABLE 1998 Commonly Treated Forms of Internal Contamination

Chelating agents such as calcium and zinc salts of diethylenetriamine pentaacetic acid (Ca-DTPA and Zn-DTPA, respectively) are effective treatments for contamination with heavy metals and rare earths that emit alpha radiation. If alpha-emitting contamination is detected in wounds or in the nares or oropharynx, treatment with DTPA should be initiated promptly, ideally within 1 to 2 h after contamination has occurred. Potential contraindications for the use of DTPA are severe renal dysfunction, thrombocytopenia, or leukopenia. DTPA is administered systemically by slow IV push or by aerosol administration. Ca-DTPA has been shown to be more effective in animal studies and is the preferred form of drug for the initial one to two days of treatment. Zn-DTPA is less toxic and recommended for treatments of longer duration and of pregnant females. For aerosol administration, Ca-DTPA is preferred because of the metallic taste associated with Zn-DTPA. Most DTPA solutions in nuclear medicine...

TABLE 1458 Pet Associated Zoonotic Infections

Cats are the host of the intracellular protozoan Toxoplasma gondii, which causes toxoplasmosis. Human toxoplasmosis can occur in three ways by ingestion of uncooked or raw meat, especially pork or mutton containing the Toxoplasma cysts by ingestion of the oocysts from cat and wild-animal feces and transplacentally.303 52 Transplacental transmission can result in congenital abnormalities of retinochoroiditis, hydrocephalus, hepatosplenomegaly, and thrombocytopenia in 10 percent of the children infected. The majority of children transplacentally infected with toxoplasmosis display no significant abnormalities. Nevertheless, pregnant women should limit their contact to only indoor cats and avoid contact with cat feces. The encysted trophozoite can become reactivated in a

Idiopathic autoimmune thrombocytopenic purpura ITP

A relatively common disorder in adults, ITP often complicates diseases associated with defective immune regulation (e.g. systemic lupus erythematosus, HIV infection, lymphoproliferative disorders, Hodgkin's disease). The onset of thrombocytopenia and bleeding is usually less abrupt than in drug-induced immune thrombocytopenia caused by-drugs other than heparin. In adults, ITP is usually chronic and seldom remits spontaneously. IgG and or IgM autoantibodies react with GPIb, GPIIb-IIIa, or other antigens present on the ITP patient's platelets, on platelets from normal donors and, sometimes, on the patient's megakaryocytes. The IgG or IgM antibodies may fix and activate complement components on platelet surfaces however, complement fixation is often incomplete, and intravascular platelet lysis is much less common than in drug-induced immune thrombocytopenia (caused by drugs other than heparin). Macrophages have specific surface receptors for the Fc portion of IgGl and IgG3 molecules, as...

Malignant Lesions Lymphoma

Non-Hodgkin lymphoma and leukemia are systemic diseases that may or may not involve the spleen. No survival benefit has been demonstrated for splenectomy in the treatment of these diseases however, splenectomy is occasionally applicable for management of symptomatic splenomegaly and for management of leukopenia or thrombocytopenia that limits medical therapy. These disorders are constituted by the deregulated proliferation of hematopoi-etic lineage cells within the bone marrow, but also may result in proliferation of blood components in former extramedullary sites of hematopoiesis, namely the liver and spleen. Myeloproliferative disorders can result in splenomegaly due to increased splenic blood flow, but can also be secondary to portal hypertension from obstructive hepatic fibrosis due to proliferation of myeloid hema-topoietic components in the liver. The treatment of myeloproliferative disorders involves the use of alkylating chemotherapeutic agents and periodic blood product...

Azathioprine

Azathioprine is a purine antagonist the active metabolite of which is 6-mercaptopurine. Although azathioprine has been used successfully to treat immune-mediated disease in cats, serious bone-marrow suppression has been reported in cats treated with doses used in dogs (2.2 mg kg and 1.1 mg kg on alternate days Beale etai, 1992). In addition to dose-related marrow toxicity, idiosyncratic severe, irreversible, fatal leucopenia and thrombocytopenia have been reported in cats. The recommended dose in cats is 1.5-3.125 mg cat every 48 h this is equivalent to about one-tenth to one-eighth of a 25 mg tablet and clearly very difficult to achieve accurately. Many authors do not recommend the use of azathioprine in cats and chlorambucil is often used as an alternative

Intravenous Access

Tissue oxygenation also requires restoration of circulating blood volume, and it is routine to place at least two large-bore intravenous lines for infusion of crystalloid and potentially blood. A practical limitation during fluid resuscitation is sometimes the size of the intravenous access, which limits the rate of infusion ( Table.27-2). The largest-bore catheter possible should be used in patients who may require aggressive fluid administration. All patients should be placed on a continuous cardiac monitor and pulse oximeter. As the intravenous lines are placed, initial blood samples should be drawn for type and cross matching, coagulation studies prothrombin time (PT), partial thromboplastin time (PTT), platelet count and a baseline complete blood count (CBC). All women of childbearing age need a pregnancy test. An immediate serum glucose assessment is critical in the patient with a depressed level of consciousness. A baseline metabolic assessment requires more extensive...

Complications

The overwhelming bulk of clinical and scientific data indicate that the infusion of resuscitation fluids is an extraordinarily safe procedure but still with risk for complications. The overall percentage of interventions that lead to complications is quite low, but given the frequency with which fluid resuscitation occurs, complications arise regularly. This is particularly true when blood products are infused and especially when they are infused in massive quantities. Although there is no strict criteria, massive transfusion is generally defined as the transfusion of the equivalent of one blood volume (70 to 80 mL kg in an adult) within 24 h. Clotting abnormalities are commonly noted after massive transfusion owing to dilutional thrombocytopenia and the effects of storage on coagulation factors and platelet number and function. Previous guidelines recommended the routine transfusion of FFP and platelets based upon the number of units of red cells transfused. It has been demonstrated,...

Ancillary Studies

While there is no specific laboratory test for the diagnosis of septic shock, tests are useful because they (1) assess the general hematologic and metabolic state of the patient, (2) provide results that suggest the potential for occult bacterial infection, and (3) detect a specific microbial etiology for infection. Basic laboratory studies should include a complete blood count including platelet count DIC panel (prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, antithrombin III concentration) serum electrolytes (including magnesium, calcium, phosphate, and serum glucose) liver function panel (bilirubin, alkaline phosphate, and ALT) renal function panel (blood urea nitrogen and creatinine) arterial blood gas analysis and urinalysis. Blood should be typed and crossed if low hematocrit is suspected. A chest radiograph should also be a part of the basic evaluation. Flat and upright abdominal films are helpful in patients in which there is a potential abdominal...

Heparin

Perioperative heparin prophylaxis can cause thrombo-cytopenia. There are two types of heparin-induced thrombocytopenia (HIT). HIT I is characterized by a transitory, slight, and asymptomatic reduction in platelet count during the first 1-2 days of treatment. It resolves spontaneously and does not require discontinuation of the drug. The origin of HIT I is not completely understood, but may be caused by a heparin-induced platelet clumping. The immunologic etiology of HIT II is largely accepted platelet factor 4 (PF4) displaced from endothelial heparin sulphate or directly from the platelets binds to the heparin molecule to form an immunogenic complex. The IgG anti-heparin PF4 immunocomplexes activate platelets and provoke an immunologic endotheli-al lesion with thrombocytopenia and or thrombosis. Cutaneous allergic manifestation at the heparin injection sites and skin necrosis may be present as well. Interestingly, hemorrhagic events are not frequent, while the major clinical...

Babesiosis

Infection with the murine strain, B. microti, is typically a mild illness in healthy people however, in the asplenic or immunocompromised patient, such as those with AIDS, lymphoma or transplant patient, the disease may be overwhelming. Infection with bovine strains B. divergens and B. bovis, as seen in Europe, occurs in asplenic patients and is often fatal. Initial symptoms of babesiosis are nonspecific and include fever, chills, nausea, vomiting, arthralgia, myalgia, headache, fatigue and dark urine. The presence of a rash similar to erythema chronicum migrans probably reflects simultaneous infection with Borrelia burgdorferi, which is transmitted by the same vector. Laboratory studies may show decreased haptoglobin, elevated reticulocytes and parasitized red cells on blood films. Leukocytosis is rare however, thrombocytopenia is common. Patients often have a positive direct Coombs test, and urine studies reveal proteinuria and hemoglobinuria. Liver function tests often show mild...

Myelopoiesis

Myelopoiesis is regulated at least in part by a series of glycoproteins referred to as hematopoietic growth factors (HGFs). Erythropoietin, produced in response to hypoxia by the peritubular adventitial cells of the kidney, is a true hormone, and G-CSF is similar in so far as the circulating levels are inversely related to the neutrophil count. Interleukin 6 (IL-6) levels also rise in neutropenic and infective states. Thrombopo-ietin, which regulattes megakaryocyte production, is of particular interest as the serum levels are largely regulated by end-organ (platelet) sequestration, and more thrombopoietin becomes available when the platelet count falls. Several other HGFs such as GM-CSF and IL-3 cannot be readily measured in the plasma and probably act in a paracrine manner. The central importance of erythropoietin in red cell production is apparent from the profound anemia that occurs in anephric individuals. Similarly, mice with knockouts of the G-CSF or thrombopoietin genes have...

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