Predictive Factors for Poor Outcome in Danaparoid-Treated HIT-Patients: A French Multicentre Case-Control Study.

Abstract

Objective: to identify predictive factors of complications and mortality in danaparoid-treated HIT-patients. Patients and Methods: case-control study involving HIT-patients defined by a relative decrease in platelet count of over 40% with or without thrombosis at presentation and positive laboratory testing (functional assay +/− ELISA). A patient presenting a complication 48 hours after heparin replacement with danaparoid (thrombosis, DIC, amputation, haemorrhage, death) was considered as a case. Results: 49 cases and 65 controls were included (mean age 67±14 y; 51% women), from cardiovascular (53%) or orthopaedic (5%) surgery, intensive care (6%) or medicine (8%) units. Mean duration to complication was 7 days (D): death (n=26); thromboses (n=23); DIC (n=6); amputations (n=4); and haemorrhages (n=8). In univaried analysis, compared to controls, cases presented: an earlier HIT (7.9±3.5 versus 10.1±7.1 D; p=0.03) a lower platelet nadir (53±37 versus 70±37 G/L ; p=0.01), a more frequent thrombosis at HIT diagnosis (59% versus 32%, p=0.004), a later heparin withdrawal after HIT diagnosis (2.8 versus 1.3 d; p=0.01), a delayed heparin replacement (3.7 versus 1.9 d ; (p=0.001), an inadequate dosage of replacement therapy (44% versus 19% ; p=0.004). In multivaried analysis, predictive factors leading for poor outcome were: an initial thrombosis at HIT diagnosis (OR=3.2 [1.3–8]), a delay greater than 48 h for replacement therapy with danaparoid (OR=6.6 [2.5–17.3]), insufficient doses of danaparoid (OR=4.3 [1.5–12]). Conclusion: this study confirms the mandatory need for a prompt replacement therapy and strict adherence to recommended doses for HIT-patients.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia

“…We found 5 nonrandomized studies that reported on DVT outcomes in patients with confirmed HIT. 17,19,65,75,76 Three cohort studies reported on symptomatic lowerextremity proximal DVT. 17,19,75 One study reported on symptomatic upper-extremity DVT.…”

“…19 Two cohort studies reported on asymptomatic HIT patients who were screened for silent DVT. 65,76 The EtD framework is shown online at https://dbep.gradepro.org/profile/ 52FE6F09-0233-F65B-BA7A-5ADB96E1007D.…”

“…Ultrasound studies identified silent lower-extremity DVT in 12% to 44% of asymptomatic HIT patients. 65,76 The panel agreed that the benefits of lower-extremity screening in patients with acute isolated HIT are moderate because of the high prevalence of silent DVT and the high risk of pulmonary embolism with proximal DVT.…”

Dynamic intercellular redistribution of HIT antigen modulates heparin-induced thrombocytopenia

“…Heparin-induced thrombocytopenia (HIT) is an iatrogenic disorder characterized by thrombocytopenia and a high risk of limb-or lifethreatening thrombosis. [1][2][3] Pathogenic HIT antibodies react with a multimolecular complex of platelet factor 4 (PF4) and polyanions such as heparin or cell-surface glycosaminoglycans. 4,5 Immuglobulin G-containing immune complexes involving PF4 bound to membrane chondroitin sulfate (CS) activate platelets through FcgIIA receptors, 5,6 contributing to the risk of thrombosis.…”

Vaccine-induced immune thrombotic thrombocytopenia: what we know and do not know

“…These atypical sites of thrombosis in VITT stand in distinction to those in HIT and aHIT, where thromboses occur in more typical locations, such as deep venous thrombosis, pulmonary embolism, and/or arterial thromboses. [29][30][31][32] The laboratory features of VITT indicate a consumptive coagulopathy (thrombocytopenia, low fibrinogen, and elevated Ddimer), which is only seen in the most severe cases of HIT. 33 When performed, tests for acquired thrombophilias such as antiphospholipid antibodies, paroxysmal nocturnal hemoglobinuria, ADAMTS13 deficiency, and myeloproliferative neoplasms are usually normal.…”