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Using patients with polycythemia vera (PV) as an experimental model, we evaluated the impact of clot retraction (CR) and architecture of the clot on fibrinolysis. We studied the kinetics of clot retraction and the fibrinolysis rate in whole blood from 48 PV patients and 48 healthy controls. Measurements were performed before and after isovolemic eryhrocytapheresis (ECP). CR was measured by optical method. Clot lysis time (CLT) and maximum clot firmness (MCF) were measured by thromboelastometry in recalcified blood supplemented with t-PA and tissue factor. Compared with healthy controls, CR rate in PV patients was higher (0.0219 vs. 0.0138; p<0.001), the clot volume smaller and MCF elevated (64 vs. 58 mm). CR rate correlated with platelet count (r=0.546; p=0.001) but not with erythrocyte concentration (r=0.192; p>0.3). Compared with healthy controls, CLT in PV patients was significantly prolonged (158 min vs. 71 min). Fibrinolysis rate inversely correlated with CR rate (r=-0.566; p<0.001); MCF (r=-0.704; p<0.001) and platelet count (r=-0.461; p<0.001). As judged by confocal microscope, in comparison to healthy controls, clots formed in blood from PV patients demonstrated booth a distinctly higher degree of crosslinking and possessed thinner fibers. Altered CR, MCF and fibrinolysis speeds were not normalized following the ECP procedure. Tirofiban (a blocker of platelet GPIIb/IIIa receptors), unlike aspirin, normalized abnormal CR and fibrinolysis in blood from PV patients. Collectively, our data indicate that in PV patients, abnormal CR may result in formation of thrombi that are more resistant to fibrinolysis. ECP and aspirin failed to normalize platelet-related fibrinolysis resistance., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We tested the hypothesis that hypertension associated with polycythemia vera (PV) may be related to hemoglobin released from erythrocytes (cell-free hemoglobin, fHb). We assessed hematocrit, mean arterial pressure (MAP), blood viscosity, and the level of fHb and nitrite/nitrate (NOx) in the plasma of 73 PV patients and 38 healthy controls. The effect of isovolemic erythrocytapheresis (ECP) on the considered parameters was also studied. From the whole group of PV patients a subset of subjects with normal (normotensive patients, n = 16) and elevated MAP (hypertensive patients, n = 57) can be subtracted. It was found that in comparison with healthy controls, PV patients have significantly (p ≤ 0.01) elevated Hct (0.567 vs. 0.422), blood viscosity (5.45 vs. 3.56 cP), MAP (106.8 vs. 93.8 mmHg), plasma fHb (9.7 vs. 2.8 mg/dL), and NOx levels (34.1 vs. 27.5 μM). Compared with normotensive patients, hypertensive PV patients demonstrated a higher rise in fHb (10.2 vs. 8.0) and plasma NOx levels (35.8 vs. 31.0). In PV patients, fHb positively correlates with MAP (r = 0.489), NOx levels (r = 0.461), hematocrit (r = 0.428), and viscosity (r = 0.393). Blood viscosity positively correlated with hematocrit (r = 0.894), but not with other considered parameters. In PV patients MAP poorly correlated with hematocrit, whereas the correlation between MAP and NOx altered from - 0.325 (healthy control) to + 0.268 (PV patients). ECP procedure was associated with a significant (p < 0.01) reduction of hematocrit, fHb, blood viscosity, and MAP. In the normotensive subgroup of PV patients the ECP procedure did not affect MAP. It can be concluded that accelerated scavenging of nitric oxide by fHb rather than high Hct may be a key factor determining the development of hypertension in PV patients.

Polycythemia vera (PV) is associated with an increased frequency of thrombotic complications. This study was undertaken to evaluate the hemostatic balance in the blood of PV patients by means of thromboelastography (TEG). The effect of isovolemic erythrocytapheresis (ECP) on the hemostasis of PV patients was also studied. We assessed the coagulation status of 76 PV patients undergoing ECP and 50 of healthy controls. TEG measurements were performed immediately before and after the ECP procedure. Coagulation was triggered by recalcification in freshly collected citrated blood. We recorded clotting time (R), alpha angle, and maximum amplitude (MA) of the clot. The results presented here show that, compared with healthy controls, PV patients demonstrated an increase in alpha angle (p<0.005) and in MA (p=0.14). In the subgroup of PV patients with high (>440 × 10(9)l(-1)) platelet (PLT) count, differences in MA (p<0.01) and alpha angle (p<0.001) were more significant. Following ECP procedure, a significant (p ≤ 0.01) reduction of R time, a rise of alpha angle, and MA were observed, indicating augmentation of a hypercoagulable state. In PV patients, the rise in alpha angle positively correlated (r=0.549) with platelet count but not with the number of erythrocytes and leukocytes. Following ECP, this correlation was reduced (r=0.382). Dilution (with saline) of blood from PV patients and of healthy controls, to a degree similar to that used during the ECP procedure, resulted in reduction of R and rise of the alpha angle. In conclusion, TEG measurements show that the majority of PV patients demonstrate abnormal hemostasis in which a major role is played by platelets rather than plasma factors. The hypercoagulable state in PV patients is significantly augmented following the ECP and may be related to the hemodilution intrinsically included in this procedure. TEG may help to assess the thrombotic risk in individual PV patients.