Search

Congenital causes of venous thrombosis have gained increasing prominence with the description of the factor V Leiden mutation and the prothrombin gene mutation. More recently, the description of the association between increased levels of coagulation factors and venous thrombosis and the finding that patients with thrombophilia can harbor more than one prothrombotic state have further increased the clinical relevance of the congenital thrombophilic states. In this qualitative review, we summarize current knowledge of the congenital prothrombotic states and propose a simple classification system that divides the states into two broad groups: those associated with reduced levels of the inhibitors of the coagulation cascade and those associated with increased levels or function of the coagulation factors. The first group is less common than the second, but it is associated with a much higher risk for venous thrombosis. This review provides clinicians with an evidence-based, practical guide to the congenital prothrombotic states.

Heparin-induced thrombocytopenia is a prothrombotic drug reaction caused by platelet-activating antibodies that recognize complexes of platelet factor 4 and heparin.To describe a syndrome termed delayed-onset heparin-induced thrombocytopenia, in which thrombocytopenia and thrombotic events begin 5 or more days after withdrawal of heparin.Case series.Secondary and tertiary care hospitals.12 patients who presented with serologically confirmed, delayed-onset heparin-induced thrombocytopenia, including 6 outpatients presenting after hospital discharge.The platelet serotonin-release assay was used to measure IgG-induced heparin-dependent and heparin-independent platelet activation; an enzyme immunoassay that detects IgG against platelet factor 4-heparin complexes was also used.Patients with delayed-onset heparin-induced thrombocytopenia presented with thrombocytopenia and associated thrombosis a mean of 9.2 days (range, 5 to 19 days) after stopping heparin therapy. Nine patients received additional heparin, with further decrease in platelet counts. Compared with controls, patients with delayed-onset heparin-induced thrombocytopenia had higher titers of IgG antibodies to platelet factor 4-heparin and greater IgG-induced heparin-dependent and heparin-independent platelet activation.Delayed-onset heparin-induced thrombocytopenia should be suspected when patients present with thrombocytopenia and thrombosis up to 3 weeks after exposure to heparin. This syndrome could be caused by high titers of platelet-activating IgG induced by heparin.

Platelet-mediated arterial occlusion is a well-recognized cause of limb loss in patients with heparin-induced thrombocytopenia. However, the syndrome of distal ischemic necrosis complicating the deep venous thrombosis (venous limb gangrene) sometimes associated with heparin-induced thrombocytopenia has not been well characterized.To study the pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia.Characterization (based on descriptive and case-control studies) of a novel syndrome of limb loss and hypothesis testing by analysis of plasma samples.Five university-associated hospitals in one medical community.Clinical and laboratory records of 158 patients with heparin-induced thrombocytopenia were reviewed to identify patients with venous limb gangrene (n = 8), limb arterial thrombosis (n = 10), and uncomplicated deep venous thrombosis (n = 58).Clinical and laboratory factors associated with venous limb gangrene, including thrombin-antithrombin complexes and vitamin K-dependent procoagulant and anticoagulant factors.Warfarin treatment was more frequently associated with venous limb gangrene than with limb arterial thrombosis (8 of 8 patients compared with 3 of 10 patients; P = 0.004). The anticoagulant effect of warfarin seemed greater in the 8 patients with venous limb gangrene than in the 58 patients who did not develop gangrene (median International normalized ratio, 5.8 compared with 3.1; P0.001). Compared with plasma from controls, plasma from patients with venous limb gangrene had a higher ratio of thrombin-antithrombin complex to protein C activity during warfarin treatment. No hereditable abnormalities of the protein C anticoagulant pathway were seen in any patient.Warfarin treatment of deep venous thrombosis associated with heparin-induced thrombocytopenia is a possible cause of venous limb gangrene, perhaps because of acquired failure of the protein C anticoagulant pathway to regulate thrombin generation.

To assess whether splenectomy done during hematologic remission reduces the relapse rate in patients with relapsing thrombotic thrombocytopenic purpura.Consecutive case series.Tertiary care teaching hospital.6 consecutive patients seen during a 10-year period who had had one or more relapses of thrombotic thrombocytopenic purpura.All patients had elective splenectomy while in hematologic remission and were followed after surgery for as long as 8.0 years.Attack rates (events per year) were calculated for each patient from time of presentation to time of splenectomy and from time of splenectomy to January 1996.A total of 26 episodes of thrombotic thrombocytopenic purpura occurred over 22.3 patient-years before splenectomy. After splenectomy, 3 acute episodes occurred over 22.7 patient-years. The attack rate (+/-1 SD) decreased from 2.3 +/- 2.0 events per year to 0.1 +/- 0.1 events per year.In patients who have had one or more relapses of thrombotic thrombocytopenic purpura, splenectomy done during hematologic remission reduces the frequency of acute relapse and the resulting need for medical therapy.

To determine the role of splenic radiation as a treatment for immune thrombocytopenia.Retrospective analysis of an open, nonrandomized investigation.A regional cancer center, referred care, and primary care settings.Eleven older patients with idiopathic thrombocytopenic purpura (ITP) and 8 patients with secondary immune thrombocytopenia refractory to corticosteroid treatment for whom surgery would have posed a high risk.A short course (1 to 6 weeks) of radiation therapy to the spleen (total dose, 75 to 1370 cGy) with or without concurrent and postradiation corticosteroid administration.Efficacy was assessed by measuring any increase in the platelet count and by monitoring the duration of response and side effects.Of 11 patients with ITP, 8 patients responded. Three patients had a sustained (greater than 52 weeks) increase in the platelet count to safe levels after therapy was discontinued. An additional patient had a sustained response but required intermittent, low-dose corticosteroids. Four other patients had increases in their platelet counts that lasted from 8 to 25 weeks. Two of the eight patients without ITP had a positive response, whereas four did not respond, and two were not evaluable. Patients had no adverse reactions to the radiation treatment.Splenic radiation can be a safe and effective method to raise the platelet count in older patients with ITP that is refractory to corticosteroids and in whom the risks associated with splenectomy are high.

Excerpt In healthy persons, the coccidioidal protozoan,Cryptosporidium, can inhabit the microvillous border of intestinal epithelial cells and cause an acute self-limited diarrhea. In contrast, the...

A sensitive and specific test was used to identify a platelet-agglutinating factor in sera from patients with thrombotic thrombocytopenic purpura. Serum from patients plus a preparation rich in large multimers of factor VIII: von Willebrand factor were added to target platelets, and agglutination occurred in 41 of 48 samples. Edetic acid, heparin, or heating, but not aspirin, monomeric IgG, or dansylarginine N-(3-ethyl-1,5-pentanediyl)amide inhibited the platelet-agglutinating factor. In-vitro agglutination requires the presence of a platelet-agglutinating factor and large multimers of von Willebrand factor. High concentrations of either component lowers the amount of the other required for platelet agglutination. Some patients may be more susceptible to the agglutinating factor because of a congenital or acquired abnormality in processing unusually large multimers of von Willebrand factor or because of infections or inflammatory disorders that lead to increased synthesis of large multimers of von Willebrand factor.

Heparin-associated thrombocytopenia is a relatively common complication of heparin therapy occurring in approximately 5% of the patients who receive this drug. The incidence is higher with bovine heparin then with porcine heparin. Onset of heparin-associated thrombocytopenia usually occurs 6 to 12 days after initiation of treatment and by itself has a low morbidity. Heparin-associated thrombocytopenia plus arterial thrombosis can cause major complications including stroke, heart attack, and death. The incidence of heparin-associated thrombocytopenia plus arterial thrombosis is lower than that for heparin-associated thrombocytopenia alone. The diagnosis of heparin-associated thrombocytopenia remains one of exclusion, but testing for the presence of a heparin-dependent platelet-aggregating factor may prove to be useful. Analysis of the time of onset suggests a strategy for prevention. Oral anticoagulants could be started concomitantly with the heparin so that it could be discontinued in several days. This approach may prevent most episodes of heparin-associated thrombocytopenia.