Bleeding and thrombosis in patients with chronic myeloproliferative disorders (cMPD)

Backgroud: The chronic myeloproliferative disorders (cMPDs) are clonal neoplastic diseases of the bone marrow separate from acute myeloid leukemia and the dysmyelopoietic syndrome. Chronic MPD consist of 4 diseases, including polycythemia vera (PV), essential thrombocythemia (ET), agnogenic myeloid metaplasia (AMM), and chronic myelogenous leukemia (CML). Aim: The present study aimed to explore the rate of thrombotic and hemorrhagic complications in cMPD and to identify parameters that are most likely associated and/or predict the occurrence of these haemostatic complications. Patients, materials and Methods: Accordingly a total of 45 patients with various entities of chronic myeloproliferative disorders (cMPDs) were enrolled in this study (24 men and 21 women) with a mean age (± SD) of 41.35±10.9 years (range between 19 and 65 years). Of these, 36 patients had CML, six patients had PV, two patients had IMF, and one patient had ET. This study was conducted from January, 2003 to July, 2004 and involves three medical centers in Baghdad, AL-Kadhmiya Teaching Hospital, the National Center of Hematology/AL-Mustansiriya University, and Baghdad Teaching Hospital. Additionally, 25 apparently healthy individuals (13 men and 12 women) with a mean age (± SD) 42.2± 12.0 years (range between 24 and 66 years) were included as control group. The patients and healthy subjects were submitted for the following investigations; routine hematological tests including, total WBC counts, platelet counts, hemoglobin (Hb) concentration, and hematocrit (Hct); bleeding time (BT) determination by Duke's method; plasma fibrinogen concentration by clotting method of Clauss); thrombin time (TT) determination by the STA® Analyzer; plasma factor VIII:C (FVIII:C) level by activated partial thromboplastin time (aPTT) based assay; plasma factor VILAg (FVILAg) and plasma factor X:Ag (FX:Ag) levels by enzyme linked immunosorbent assay (ELISA); and plasma D-Dimers determonation by latex agglutination test. Results: The results showed that the total rate of haemostatic complications among cMPD patients was 20 %. The frequency of bleeding complications was slightly higher than that of thrombotic complications (11.1 % versus 8.9 %). The frequency of haemostatic complications were particularly high in PV (83.3 %), while it is less frequent in CML group (5.6 %) than in other cMPD groups (77.8 %), (P<0.001). The occurrence rate of thrombohaemorrhagic complications was significantly associated with increasing patients' ages (P=0.005). Additionally, the occurrence of thrombohemorrhagic complications was inversely correlated with the disease duration (r ==-315, P<0.05). Data concerning hematologic investigation revealed that Hb concentration and hematocrit values were significantly high in PV group (P<0.001), while in CML patients they were significantly lower as compared to control group (P=0.002). The median of total WBC counts were significantly higher in CML group as compared to the other cMPD groups and control (Mann-Whitney, P<0.05) Moreover, The median of total WBC counts were significantly higher in PV group as compared to the control group (Mann-Whitney, P<0.05). The median platelet count in PV group was significantly higher as compared to other cMPD groups and control (Kruskal Wallis, P<0.05). As well, Thrombocytosis was significantly associated with the occurrence of disturbed haemostasis (P<.001), and the rate of patients with thrombocytosis (>450xl09/L) was significantly higher in patients with disturbed haemostasis as compared to asymptomatic patients (x-test, P<0.001). Moreover, thrombohaemorrhagic complications were correlated with platelet count (r=0.609, P<0.001). CML patients had significantly higher plasma fibrinogen concentration than control (P<0.001), whereas, no significant differences were Observed between the other cMPD entities and control (LSD, P>0.05). Hyperfibrinogenaemia (>4 g/L) was insignificantly associated with the occurrence of haemostatic complications (P=0.4). Results showed that mean thrombin time were insignificantly different among cMPD groups (P=0.783). However, the mean thrombin time was insignificantly higher in patients with disturbed haemostasis as compared to asymptomatic patients (P=0.16). Factor VII:Ag level was found to be significantly lower in CML patients in comparison to control (P=0.001). Moreover, the mean plasma FVILAg level was insignificantly higher in patients with thrombohaemorrhagic complications than asymptomatic patients (P=0.728). Concerning the plasma factor VIIIC , FXAg levels and bleeding time, multiple statistical analyses comparing the cMPD groups and control were insignificant (P>0.05). Additionally, no association was found between any of these three parameters and the occurrence of thrombohaemorrhagic complications. The differences in the rate of positive plasma D-Dimers between patients with disturbed haemostasis and those who are asymptomatic were statistically insignificant (P=0.5).
Conclusion: Bleeding and thrombosis are frequent complications in patients with cMPD. Thrombocytosis may have an important role in the pathogenesis of thrombohaemorrhagic complications. Bleeding time alterations are uncommon abnormalities in cMPD patients. But, clinically, patients with thrombocytosis and prolonged bleeding time should be suspected of having an increased risk of bleeding. So, more clinical and laboratory efforts should be focused to achieve better understanding of the underlying mechanism that may predispose those patients for haemostatic complications.