Heparin-Induced Thrombocytopenia in Patients with Philadelphia-Negative Myeloproliferative Disorders and Unusual Splanchnic or Cerebral Vein Thrombosis

Abstract

Background: Philadelphia-negative myeloproliferative disorders (Ph-MPD) are common causes of unusual splanchnic or cerebral vein thrombosis, which is treated with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Heparin-induced thrombocytopenia (HIT) is a dangerous potential complication of this therapy, but it has rarely been reported in Ph-MPD. Patients and Methods: We retrospectively reviewed clinical records of 29 patients with Ph-MPD who have been treated with UFH or LMWH for unusual splanchnic or cerebral vein thrombosis (3 cerebral sinus, 6 portal and 20 hepatic vein). The goal of the study was to determine the occurrence of new thrombotic events during heparin therapy secondary to HIT (HITT). Results: During heparin therapy, 5 out of the 29 patients (17%) developed a new thrombotic episode (pulmonary embolism) with a high clinical probability of HIT based on the 4 T’s score even though not all the patients developed ‘true’ thrombocytopenia. A diagnosis of HIT was established in 2 patients (6.8%) through the presence of heparin-related antibodies. Conclusions: Ph-MPD patients on heparin warrant careful monitoring and HIT has to be suspected whenever platelet counts drop or a new thrombosis is detectable.

Venous thromboembolism in patients with essential thrombocythemia and polycythemia vera

“…Although the incidence of HIT probably is higher in patients treated with unfractionated heparin than lowmolecular-weight heparin, 86 the condition should not be ignored in patients treated with low -molecular-weight heparin. 86 Although good data are lacking, the incidence is probably higher in PV and ET patients than in the general population, 87,88 and the condition is harder to diagnose and probably underestimated in PV and ET patients. 71,87,88 The high platelet count in ET and PV patients demonstrate that physicians should be more attentive to platelet count variations rather than the typical thrombocytopenia threshold.…”

“…86 Although good data are lacking, the incidence is probably higher in PV and ET patients than in the general population, 87,88 and the condition is harder to diagnose and probably underestimated in PV and ET patients. 71,87,88 The high platelet count in ET and PV patients demonstrate that physicians should be more attentive to platelet count variations rather than the typical thrombocytopenia threshold. Therefore, treatment with low-molecular-heparin should be carried out carefully in these patients, keeping a potential diagnosis of HIT in mind.…”

Anti-Platelet Factor 4/Heparin Antibody Formation Occurs Endogenously and at Unexpected High Frequency in Polycythemia Vera

“…Several case reports of HIT occurring upon heparin treatment in PV and ET have been published suggesting that patients with MPN might be at risk for HIT-related immune responses and potentially thrombotic events [41, 42, 54]. HIT is a severe, prothrombotic condition facilitating arterial or venous thromboses triggered by antibody formation against PF4/heparin complexes upon treatment with heparin [31].…”

“…Importantly, thrombocytosis in PV and ET is reflective of excessive platelet production and turnover, and platelets in MPN are known to circulate in an activated state, thus providing ample PF4 which could promote the formation of anti-PF4/heparin antibodies in PV and ET [17]. A limited number of PV and ET patients with occurrence of HIT have been reported (Table 1) [41–53]. In addition, analysis of a cohort of HIT patients found overrepresentation of ET and PV with 4.7% (2/42) [54].…”

“…The true incidence of HIT in PV and ET has not been clearly assessed given the masking of thrombocytopenia by excessive platelet production and the scarcity of the literature on this topic limited to a handful of case reports and series. A comprehensive case series studying 29 MPN patients [41] observed strong clinical evidence for HIT in five patients, but only two were tested for anti-PF4/heparin antibodies. Therefore, we employed a systematic approach to assess PF4/heparin antibody formation and its significance for thrombosis in a large cohort of PV and ET patients given their high thrombotic risk.…”