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©2013 Baishideng.
World J Hematol. May 6, 2013; 2(2): 20-43
Published online May 6, 2013. doi: 10.5315/wjh.v2.i2.20
Published online May 6, 2013. doi: 10.5315/wjh.v2.i2.20
Table 1 A Platelet kinetic, hemostatic and thromboxane B2 studies in normal individuals (control), asymptomatic essential thrombocythemia patients (E-), essential thrombocythemia patients suffering from erythromelalgia (E+) and the effect of acetylsalicylic acid (aspirin) in E+ patients
Study population | Control healthy | ET | ||
E- | E+ | E+ treated | ||
Aspirin treatment | No | No | No | Yes→E |
Platelet kinetic study[22] | ||||
Patients (n) | 6 | 10 | 10 | 7 |
Platelet survival (d) | 8.0 ± 0.41 | 6.6 ± 0.31 | 4.2 ± 0.41 | 6.9 ± 0.4 |
Hemostatic studies[24] | ||||
Patients (n) | 20 | 16 | 5 | 5 |
Platelet count (× 109/L) | 256 ± 10 | 671 ± 66 | 689 ± 1051 | 857 ± 52 |
Platelet activation markers | ||||
Thrombomoduline (ng/mL) | 40 ± 2.1 | 73 ± 41 | 90 ± 101 | 64 ± 12 |
PF4 (IU/108 plts) | 1.6 ± 0.11 | 2.9 ± 0.51 | 9.1 ± 5.01 | 4.3 ± 3.3 |
β-TG (IU/108 plts) | 16 ± 1.2 | 37 ± 6.6 | 128 ± 33 | 29 ± 15 |
Coagulation activation markers | ||||
F1+2 (nmol/L) | 1.3 ± 0.1 | 1.2 ± 0.1 | 1.2 ± 0.4 | 1.1 ± 0.3 |
FDP (ng/mL) | 669 ± 31 | 707 ± 51 | 702 ± 83 | - |
Table 2 Clinical manifestations and sequence of aspirin-responsive microvascular cerebral ischemic attacks in each of 17 patients with essential thrombocythemia
Patient nubmer | |||||||||||||||||
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | |
Thrombotic events sequence | MI | VS | CS | VS | MI | VS | CS | CS | CS | E | CS | CS | E | CS | CS | VS | CS |
CS | E | VS | CS | VS | E | AP | VS | VS | VS | AP | E | CS | E | E | CS | E | |
E | CS | CS | |||||||||||||||
AP | E | ||||||||||||||||
MI | |||||||||||||||||
Time lapse of sequential thrombotic events (yr) | 2 | 5 | 2 | 3 | 5 | 4 | 1 | 3 | 1 | 7 | 4 | 3 | 2 | 1 | 3 | 1 | 4 |
Cerebral and visual symptoms | |||||||||||||||||
Transient hemiparesis | + | + | + | + | + | + | + | ||||||||||
Unstable gait | + | + | + | + | + | + | + | + | + | + | + | + | + | ||||
Dysarthria | + | + | + | + | + | + | + | + | |||||||||
Transient monocular blindness | + | + | + | ||||||||||||||
Scintillating scotomata | + | + | + | + | |||||||||||||
Blurred vision | + | + | + | + | + | + | + | + | + | + | |||||||
Headache | + | + | + | + | + | + | + | + | + | + | |||||||
Number of attacks | S | M | S | S | M | S | S | F | S | F | S | S | F | S | F | M | S |
Table 3 Incidence of thrombotic and bleeding complications in the prospective 1975-1996 Rotterdam study of 68 essential thrombocythemia patients during a median follow-up of 6.7 years according to treatment strategy n (events/100 persons per year)
Treatment strategy | Duration of follow-up (person/yr) | Thrombotic complication | Bleeding complications |
Asymptomatic (14 patients) | |||
Watchful waiting | 127 | 27 (33.3) | 2 (1.6) |
Symptomatic (54 patients) | |||
Low dose aspirin | 139 | 5 (3.6) | 10 (7.2) |
Platelet reduction | 113 | 10 (8.9) | 2 (1.8) |
Low dose aspirin + platelet reduction | 40 | 0 (0) | 4 (10) |
Total | 419 | 42 (100) | 18 (100) |
Table 4 Nature of neurological and visual, aspirin responsive migraine-like microvascular cerebral ischemic attacks in 56 reported cases of essential thrombocythemia n (%)
ET-related clinical manifestations | Relative incidence |
Acroparesthesia or numbness | 13 (24) |
Painful toes and/or cyanosis (Erythromelalgia) | 12 (21) |
Transient ocular attacks | |
Visual scotomas | 11 (20) |
Amaurosis fugax | 5 (9) |
Diplopia | 3 (5) |
Hemianopsia | 2 (4) |
Blurred vision | 14 (25) |
Transient ischemic attacks TIAs or hemiparesis arm and/or leg | 17 (30) |
Atypical TIAs total | 31 (55) |
Aphasia | 3 (5) |
Dysarthria | 12 (21) |
Unsteadiness or unstable gait | 16 (29) |
Functional symptoms | |
Pulsatile headache | 26 (46) |
Syncope | 3 (5) |
Vertigo | 2 (4) |
Dizziness | 3 (5) |
Seizures | 3 (5) |
Organic mental syndrome | 1 (2) |
Table 5 Incidence of thrombosis in polycythemia vera and essential thrombocythemia patients
PV | ET | |||
GISP | Marchioli | Cortelazzo | Carobbio | |
Patients number | 1213 | 1638 | 100 | 439 |
Age group (yr) | ||||
< 40 | 1.8 | 2.1 | 1.7 | NA |
40-60 | 2.8 | NA | 6.3 | NA |
> 65 | 5.1 | 4.9 | 15.1 | 2.3 |
Previous | ||||
Thrombosis | 4.8 | 5.0 | NA | 2.3 |
Table 6 Low, intermediate and high thrombohemorrhagic risk stratification of essential thrombocythemia patients and a flexible approach towards therapeutic implications with reference to platelet counts including essential thrombocythemia patients with features of early polycythemia vera in blood and bone marrow (prodromal polycythemia vera)
Platelets (400-1500 × 109/L) | Platelets (400-1000 × 109/L) | Platelets (400-1000 × 109/L) | Platelets (> 1500 × 109/L) |
Low risk | Low risk | High risk | High risk |
Completely asymptomatic | Microvascular disturbances only1 | Major thrombosis, and/or bleeding | > 1000 × 109/L and minor thrombosis/bleeding = high |
No vascular risk | No vascular risk | Vascular risk | No vascular risk |
No bleeding risk | No bleeding risk | ||
Age < 65 yr2 | Age < 65 yr except2 | Age > 65 yr except3 | All ages |
Aspirin uncertain | Low dose aspirin | Platelet reduction to normal or near normal | Platelet reduction to < 1000 × 109/L |
Wait and see? | 50 to 100 mg/d | ||
Intermediate risk | |||
Aspirin primary prevention? | Microvascular disturbances and platelet count between 1000 and 1500 × 109/L with clear indication aspirin1, →side effects (platelet reduction) | Continue aspirin1 | When platelets < 1000 × 109/L add aspirin |
ET patients and their physician usually prefer the use of low dose aspirin |
Table 7 Platelet count and incidences of thrombotic and hemorrhagic complications in 809 patients with essential thrombocythemia from 11 retrospective studies n (%)
No. of ET patients | 809 (100) |
Age (yr), mean (range) | 54 (6-90) |
Platelet mean (× 109/L) | 1050 |
Thromboembolic complications | 466 (58) |
Microvascular attacks/thrombosis | 333 (41) |
Peripheral total | 197 (24) |
Acroparesthesias/erythromelalgia | 168 (21) |
Acrocyanotic ischemia/gangrene | 77 (9.5) |
Cerebral total | 138 (17.1) |
Headache/dizziness | 59 (7.3) |
Atypical TIAs typical TIAs | 46 (5.7) |
Visual disturbances | 15 (1.9) |
Not specified | 18 (2.2) |
Major arterial thrombosis | 164 (20) |
Lower extremity | 61 (7.5) |
Carotic/cerebral | 52 (6.4) |
Cardiac | 44 (5.4) |
Others | 15 (1.9) |
Venous thrombosis | 33 (4) |
Leg/pelvis vein thrombosis | 27 (3.3) |
Portal/splenic vein thrombosis | 8 (1) |
Budd Chiari syndrome | 0 (0) |
Hemorrhages total | 134 (17) |
Minor: Bruises, ecchymoses, epistaxis | |
Gum bleeding, bleeding after trauma | 105 (13) |
Major: gastrointestinal tract bleeding, large hematomas | |
Hemarthrosis and others | 29 (3.6) |
Table 8 Vascular complications, hematocrit and platelet counts in 65 patients with classical polycythemia vera at time of presentation and during follow-up treatment: results from a retrospective observational study 1985
At presentation | After treatment | |
No. of PV patients | 65 | 65 |
Follow-up | - | 225 patient-years |
Hematocrit | 0.60 (0.49-0.74) | < 0.48 before 1975 |
< 0.45 since 1975 | ||
Platelet count (× 109/L) (mean) | 512 | 390 |
Major vascular occlusive events | 49% | 35% |
Microvascular/large vessels | 13/19 (not specified) | Specified |
Cerebrovascular events mainly TIA | - | 15 |
Superficial thrombophlebitis | ||
or venous thrombosis | - | 20 |
Microvascular disturbances | - | 5 |
Myocardial infarction | - | 1 |
Mesenteric vein thrombosis | - | 1 |
ECLAP study patient populations | n (%) |
Observational study[91]: n = 1112 of which 66% on aspirin | |
RCT low dose aspirin vs placebo[75]: n = 518 of which 50% on aspirin | |
Total number of PV patients[90,91] | 1630 (100) |
On aspirin observational study plus trial | 990 (61) |
Previous thrombosis | 636 (39) |
Overall results, follow-up 2.7 yr | |
Fatal thrombosis | 67 (4.1) |
Cardiovascular disease | 35 (2.9) |
Stroke | 13 (0.8) |
Pulmonary embolism | 6 (0.4) |
Non-fatal thrombosis | 187 (11.4) |
Arterial | 90 (5.5) |
Transient ischemic attacks | 33 (2.0) |
Stroke | 23 (1.4) |
Peripheral arterial thrombosis | 20 (1.2) |
Myocardial infarction | 14 (0.9) |
Venous | 97 (5.9) |
Superficial thrombophlebitis | 46 (2.8) |
Deep vein thrombosis | 38 (2.3) |
Pulmonary embolism | 13 (0.8) |
Total fatal and non-fatal thrombosis | 254 (15.5) |
- Citation: Michiels JJ, Ten Kate FW, Koudstaal PJ, Van Genderen PJ. Aspirin responsive platelet thrombophilia in essential thrombocythemia and polycythemia vera. World J Hematol 2013; 2(2): 20-43
- URL: https://www.wjgnet.com/2218-6204/full/v2/i2/20.htm
- DOI: https://dx.doi.org/10.5315/wjh.v2.i2.20