Pathomorphological aspects of heparin-induced thrombocytopenia II (HIT-II syndrome)

Abstract

The therapeutic use of heparin results in thrombocytopenia in 5-30% of patients. In 0.1-1% of patients treated with heparin, the platelet count decreases to between 100 x 10(9)/l and 50 x 10(9)/l and leads to severe synchronous central arterial and venous thrombosis with a mortality of 18-36%. This is known as "white-clot syndrome" or heparin-induced thrombocytopenia II (HIT-II syndrome). Whilst the clinical aspects and the central type of thrombosis in HIT-II syndrome are well documented, the histomorphology and differential diagnosis of thrombosis are not. We report three cases of HIT-II syndrome with thrombosis of the central arteries and veins. The HIT-II thrombi could be differentiated from thrombi of other origins, particularly from mural thrombi. Heparin-induced thrombi were seen on microscopical examination to be like onion skin in structure, and immunohistochemistry showed that they had a markedly reduced content of fibrin and clearly enhanced amounts of IgG and IgM. The layered structure thus implied appositional growth. The thrombi in HIT-II syndrome do not seem to be induced by activation of the coagulation cascade, but by platelet aggregation mediated by anti-platelet antibodies.

Consumption of raw brown onions variably modulate plasma lipid profile and lipoprotein oxidation in pigs fed a high‐fat diet

“…42 Various garlic extracts have been shown to decrease the activities of NADPH-producing enzymes and of fatty acid synthetase in vitro and in vivo. 17,18,43 It has also been postulated that the plasma TG lowering effect may also be, in part, due to decreases in intestinal microsomal TG transfer protein mRNA 44 and apolipoprotein B100 secretion. 14 Over-production of apolipoprotein B100 containing lipoproteins can lead to atherosclerosis and coronary heart disease and also induces hyperlipidaemia.…”

A Case of Heparin-Induced Thrombocytopenia With Sepsis and Congestive Heart Failure-First Autopsy Report in Japan-

“…In the present case, both septic DIC and HIT-induced DIC explain the clinical findings. In either case, the white clot thrombosis [12][13][14][15] of this case was compatible with HIT plus DIC.…”

“…Immunohistochemistry using anti-platelet antibody (CD41) confirmed platelet-rich thrombus, not fibrin-rich thrombus (Fig 3A,B). These pathological and immunohistochemical findings ware compatible with HIT, [12][13][14][15] although none of these findings was specific to HIT. Multiple organ necrosis suggesting DIC was not observed.…”

Intra-Arterial Eptifibatide in the Management of Thromboembolism during Endovascular Treatment of Intracranial Aneurysms: Case Series and a Review of the Literature

“…The combined use of an antiplatelet and a fibrinolytic agent suggests that in HIT II the thrombi may be more complex in their composition than initially believed. Thrombi in HIT II were previously characterized as almost entirely rich in platelets with limited fibrin content [32]. However, serum from patients with HIT II can interact with endothelial cells and promote the release of tissue factor and trigger the coagulation cascade; this effect was blocked in the presence of a glycoprotein IIb/IIIa antagonist, suggesting that activated platelets play a key role in triggering the coagulation cascade in HIT II [33].…”