Thrombotic Complications in Ph'-Negative Myeloproliferative Neoplasms - 10-Year Experience of A Medical Center in Asian Area

Totally 361 patients were collected, including 135 (37%) cases of polycythemia vera (PV), 167 (46%) cases of essential thrombocythemia (ET) and 59 (16%) cases of primary myelofibrosis (PMF). The positive rates of JAK2^V617F mutation were 90%, 65%, and 75% for PV, ET and PMF, respectively (PV vs. ET, p<0.001).

PV was associated with higher incidence of transformation to myelofibrosis compared with ET (9% vs. 3%, p=0.027) and also higher level of white blood cell count (WBC) (mean 15018/ul, 95% confidence interval (CI):13655–16381/ul; PV vs. ET, p=0.005; PV vs. PMF, p=0.001 ), higher bone marrow cellularity (bone marrow cellularity more than 60%: PV,89%; ET,70%; PV vs. ET, p=0.026; PMF,76%), and more frequent hypertension (PV, 50%; ET, 43%; PMF 19%; PV vs PMF, p<0.001; ET vs. PMF, p=0.001).

ET was associated lower incidence of coagulopathy with prolonged INR in prothrombin time (ET, 19%; PV, 36%; PV vs. ET, p=0.001; PMF, 44%; ET vs. PMF, p=0.001). PMF was associated with higher incidence of leukemia transformation(PMF,15%; PV,3.7%; ET, 2.4%; PV vs. PMF, p=0.012; ET vs. PMF, p=0.001), higher incidence of coagulopathy with prolonged aPTT (PMF,51%; PV,37%;ET, 30%; ET vs. PMF, p=0.012), increased reticulin fiber(moderate increased reticulin fiber: MF,92%; PV,44%; PV vs. PMF, p<0.001; ET, 48%;ET vs. PMF,p<0.001) and splenomegaly (mean 17.3cm, 95% CI:15.8–18.4cm, p<0.001).

Venous thromboembolism occurred in 6.4% of these MPN patients with incidence of 7.4%, 6.6% and 3.4% in patients of PV, ET and PMF, respectively. Arterial thrombosis developed in 20% of these MPN patients with incidence of 28%, 17%, and 10% in patients of PV, ET and PMF, respectively. (Table1)

Majority of venous thromboembolism presented as deep vein thrombosis (DVT) /pulmonary embolism (PE) and portal or splenic vein thrombosis with an incidence of 1.7/1.1% and 2.2%, respectively. The most common arterial thrombotic events was ischemic stroke, followed in order by ischemic heart disease, peripheral artery occlusive disease (PAOD), and ischemic bowel disease with an incidence of 14%, 9%, 3.0% and 1.1%, respectively. (Table1)

The probability of thrombosis-free survival in these 361 patients was 85%, 78% and 70% at 1, 3 and 10 year, respectively (Figure 1).

Figure 1

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Figure 1

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In terms of arterial and venous thromembolism altogether, univariate risk factor analysis revealed several risk factors including a positive JAK2^V617F, diagnosis of PV, WBC more than 16000/ul, hemoglobin level higher than 16 mg/dl, albumin level less than 4.0 g/dl, LDH higher than 250U/L, congestive heart failure(CHF),hypertension(HTN) and diabetes mellitus. With multivariate analysis, however, only WBC more than 16000/ul (Odds ratio: 3.556,95% CI:1.287–9.822,p=0.014) remained as the most significant risk factors for thromoboembolism.

Arterial thromboses are quite common in patients of MPN, especially PV. In these MPN patients, the risk of venous thrombosis including thrombosis at unusual sites is also markedly increased. The most important risk factor predisposing to vascular thrombosis (vein and artery) is WBC more than 16000/ul. Our results provide informative clinical data for management of Asian patients with MPN and facilitate further study of these disorders in this area.

No relevant conflicts of interest to declare.