Malaria-Induced Immune Thrombocytopenia

Abstract. On return from Liberia, a previously healthy 36-year-old man showed signs of malaria accompanied by severe haemolysis and slight thrombocytopenia. We found evidence of a platelet-associated IgG being responsible for the thrombocytopenia, inasmuch as the direct platelet suspension immunofluorescence test was strongly positive, the indirect immunofluorescence test and tests for drug-dependent antibodies at the same time being negative. We suggest that autoimmunity may be a contributing mechanism for platelet destruction in acute malaria.     

Drug-induced Immune Thrombocytopenia

SUMMARY. Immune thrombocytopenia is a relatively common problem associated with the clinical usage of drugs. Drugs frequently implicated include quinine, quinidine, heparin, penicillins, cephalosporins, co-trimoxazole, gold and D-penicillamine. Bleeding including bruising and purpura is the usual clinical manifestation except in immune heparin-induced thrombocytopenia in which thrombosis occurs more frequently than bleeding. Cessation of the offending drug is the important step in the treatment but other measures may also be required such as platelet transfusion and steroid therapy for patients with clinical bleeding or antithrombotic therapy with warfarin and dextran or low molecular weight heparin/heparinoid for patients with heparin-induced thrombocytopenia and thrombosis. Idiosyncratic drug-induced thrombocytopenia is mediated by an antibody which binds to platelets only in the presence of the drug resulting in the clearance of sensitised platelets by the reticuloendothelial system. In quinine/quinidine-induced thrombocytopenia, the antibodies recognise drug-dependent epitopes on platelet membrane glycoproteins Ib-IX and/or glycoproteins IIb-IIIa. In immune heparin-induced thrombocytopenia the current data suggest a mechanism which probably involves the binding of heparin-antibody complexes to the platelet Fc receptors but the precise mechanism is yet to be fully characterised. The associated thrombosis in this condition is likely to be due to platelet activation and possibly endothelial cell damage induced by the heparin-related antibody.     

Isoniazid-induced Immune Thrombocytopenia

Drug-induced thrombocytopenia occurs through immune-mediated platelet destruction, and its management is challenging during tuberculosis treatment. Although rifampicin is the most common drug causing thrombocytopenia, isoniazid can also cause thrombocytopenia. We herein report a 75-year-old man who developed thrombocytopenia during tuberculosis treatment. Platelet-associated immunoglobulin G and a drug-induced lymphocyte stimulation test for isoniazid were positive; no other causes of thrombocytopenia were identified. The patient was diagnosed with isoniazid-induced immune thrombocytopenia, and the platelet count normalized after isoniazid discontinuation. We describe the immunological mechanism of thrombocytosis due to isoniazid, an uncommon cause of thrombocytopenia that physicians should be aware exists.     

Drug-induced Immune Thrombocytopenia

SUMMARY.

Immune thrombocytopenia is a relatively common problem associated with the clinical usage of drugs. Drugs frequently implicated include quinine, quinidine, heparin, penicillins, cephalosporins, co-trimoxazole, gold and D-penicillamine. Bleeding including bruising and purpura is the usual clinical manifestation except in immune heparin-induced thrombocytopenia in which thrombosis occurs more frequently than bleeding. Cessation of the offending drug is the important step in the treatment but other measures may also be required such as platelet transfusion and steroid therapy for patients with clinical bleeding or antithrombotic therapy with warfarin and dextran or low molecular weight heparin/heparinoid for patients with heparin-induced thrombocytopenia and thrombosis. Idiosyncratic drug-induced thrombocytopenia is mediated by an antibody which binds to platelets only in the presence of the drug resulting in the clearance of sensitised platelets by the reticuloendothelial system. In quinine/quinidine-induced thrombocytopenia, the antibodies recognise drug-dependent epitopes on platelet membrane glycoproteins Ib-IX and/or glycoproteins IIb-IIIa. In immune heparin-induced thrombocytopenia the current data suggest a mechanism which probably involves the binding of heparin-antibody complexes to the platelet Fc receptors but the precise mechanism is yet to be fully characterised. The associated thrombosis in this condition is likely to be due to platelet activation and possibly endothelial cell damage induced by the heparin-related antibody.     

Immune Thrombocytopenia Induced by Cotrimoxazole

Summary: Immune thrombocytopenia induced by cotrimoxazole. A. L. Barr and M. Whineray. Aust. N.Z. J. Med ., 1980, 10 , pp. 54–55.
Cotrimoxazole administration is occasionally associated with thrombocytopenia. Interference with folate metabolism has been postulated.² The drug has also been postulated to induce an autoantibody by acting as a hapten³, but proof has not been forthcoming. A case is reported in which the serum has been shown to contain an anti-platelet autoantibody requiring sulphamethoxazole or cotrimoxazole for activity.     

Megakaryocytopoiesis in Experimentally Induced Immune Thrombocytopenia

The hypothesis that in immune thrombocytopenia, platelet antibody maynot only cause destruction of the circulating platelets but also depress plateletproduction by injuring the megakaryocytes of the bone marrow, was testedexperimentally.

Sustained thrombocytopenia was produced in rats by titrated injections ofa potent heteroimmune antiplatelet serum and megakaryocytopoiesis wasthen studied by the use of tritiated thymidine and bone marrow autoradiography. Rats in which the platelet count was maintained at a lower thannormal level by repeated thrombocytophereses, and other rats injected withplatelet antiserum previously absorbed with rat platelets, served as controls.

Profoundly altered patterns of megakaryocytopoiesis were found in the ratsin which thrombocytopenia was produced by the antiplatelet serum. The dataindicated a severely impaired and depressed megakaryocyte maturation and,possibly, destruction of some of the megakaryocytes during their maturationprocess. In the rats in which the platelet level was maintained low by repeatedthrombocytophereses, the pattern of megakaryocytopoiesis indicated accelerated maturation and there was also an increased megakaryocyte mass. Nodifference from normal was found in the rats receiving the platelet-adsorbed antiserum. It was concluded that the platelet antibody produced aninjurious effect on the megakaryocytes in the bone marrow, thereby depressing platelet production, and that the immune thrombocytopenia was theresult of both increased platelet destruction and defective platelet production.

Submitted on November 22, 1968 Accepted on October 3, 1969     

Neonatal Outcomes of Pregnancy with Immune Thrombocytopenia

Neonates born to mothers with immune thrombocytopenia (ITP) have an increased risk for neonatal thrombocytopenia and hemorrhagic complications. The aim of this study was to determine the maternal and neonatal outcomes of pregnancies with ITP and also to identify risk factors that predicts neonatal thrombocytopenia. We performed a retrospective analysis of 40 pregnancies with ITP and their 40 neonates. Among the 40 neonates, thrombocytopenia (platelet count of less than 150 × 10⁹/L) was detected in 15 neonates (37.5 %) whom 8 of them had severe thrombocytopenia (platelet count of less than 50 × 10⁹/L). Ten of the 15 neonates with thrombocytopenia required treatment to increase the platelet counts. There was statistically significant association between neonatal thrombocytopenia and maternal splenectomy history and maternal duration of thrombocytopenia. There was no statistically significant correlation between maternal platelet count and neonatal platelet count. Clinicians should pay special attention in these neonates because of risk for development of neonatal thrombocytopenia. Maternal and neonatal outcomes in patients with idiopathic thrombocytopenic purpura is generally good.     

Real-world Experience of Rituximab in Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is a relapsing–remitting disease often requiring more than one line of therapy. Rituximab is a recommended second-line therapy, but the real-world data on its efficacy and safety from resource constraint settings is limited. We aimed to analyze the safety and efficacy of rituximab in ITP. This is a single-center, retrospective study. This study was conducted at a tertiary care hospital in Northern India from 2005 to 2019. On audit of medical records, all patients of ITP (n-513) who had received rituximab (n-81) were screened for inclusion. Patients whose response assessment was not possible were excluded. Finally, 66 patients were analyzed using statistical packages of Python v3.7. The cumulative incidence of overall response on day 20 was 30.61%, and day 30 was 51.72%. The median time to response was 28 day (range 21–51 day). Cumulative incidence of complete response was 16.67%, and partial response 37.88%. After a median follow-up of 789 day (range 181–5260 day), the cumulative incidence of relapse was 30.32%, 36.12%, and 56.57% at 1, 2, and 5 years respectively. There was no effect of age, sex, duration of disease, lines of therapy received, and platelet count on either cumulative incidence of overall response or relapse. ANA positivity was significantly related to the better cumulative incidence of overall response (p = 0.012), but not with relapse. Infusion-related reactions were the commonest adverse event noted (n-4, grade ≥ 3 CTCAEv4). Rituximab and its generic version are safe and effective second line agent in ITP with a good overall response and sustained response.     

Isolated Severe Immune Thrombocytopenia due to Acute Brucellosis

Mild anemia and leukopenia are the most common hematologic findings in the course of acute brucellosis. However severe form of thrombocytopenia is less frequently reported. The patient was admitted to the hospital with fever, gingival bleeding, and petechial skin lesions related to severe thrombocytopenia. He was investigated for the causes of thrombocytopenia. Test results showed that Wright agglutination test was positive at 1/5120 titer, and blood culture was positive for Brucella melitensis. Finally, he was diagnosed as acute brucellosis. Rifampicin and doxycycline treatment was started on he third day of admission. A bone marrow aspiration was performed on the seventh day of admission because of severe thrombocytopenia did not response to brucellosis treatment. The result of bone marrow aspiration was consistent with idiopathic thrombocytopenic purpura. With the addition of corticosteroid treatment, his complaints resolved immediately, and thrombocyte count rose to normal range. He was discharged on the 12th day of rifampicin and doxycycline therapy, and he was successfully completed 6-week therapy. In cases of brucella induced immune thrombocytopenia, corticosteroid treatment might be useful for the prevention of bleeding complications.