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PubMedDate not supplied

Comparison of random-donor platelet concentrates prepared from whole blood units and platelets prepared from single-donor apheresis collections.

BACKGROUND: The use of fresh platelets results in better posttransfusion recovery and survival than does the use of platelets that have been stored before transfusion. Activation of platelets during preparation and storage may be one of the factors responsible for a number of storage-related changes in platelet membrane proteins. Blood centers commonly prepare platelet concentrates from both multiple units of whole blood and single-donor plateletpheresis collections. STUDY DESIGN AND METHODS: Seventeen plateletpheresis concentrates, anticoagulated with ACD, were compared to platelets prepared from whole blood from the same donor that was anticoagulated with CPDA-1 (random-donor platelets). After preparation, plateletpheresis and random-donor platelets were stored in plastic storage bags at 22 degrees C for 5 days. Platelet surface glycoproteins were examined by flow cytometry after platelets were fixed in dilute plasma with 1-percent formaldehyde and stained with fluorescein isothiocyanate-labeled monoclonal antibodies CD42b (anti-glycoprotein [GP]lb), CD41a (anti-GPllb/llla), and CD62 (anti-P-selectin). RESULTS: The binding of anti-CD42b was greater in plateletpheresis concentrates than in random-donor platelets on Days 3 and 5 (p < 0.01) of storage; binding of anti-CD62 was greater in the random-donor concentrates (p < 0.01) on Days 3 and 5. Plateletpheresis concentrate aggregation responses were greater on Day 5 (p < 0.01). To determine if the type of anticoagulant and the method of mixture with blood contributed to these changes, 10 samples were split into aliquots and prepared in two separate ways: One group of samples was prepared by allowing anticoagulant (ACD) and blood to flow into the tube at a rate of 3 microL per second, and the other group of samples was prepared by allowing blood to flow into tubes containing a measured amount of CPDA-1. The first samples bound more anti-CD42b than the second samples (p < 0.01). The second group of samples contained significantly more microvesicles that bound anti-CD41a than did the first group (p < 0.01). Samples prepared by the first method but anticoagulated with CPDA-1 contained more microvesicles but had the same amount of anti-CD42b binding as did similarly prepared samples anticoagulated with ACD (p < 0.05). CONCLUSION: Platelet concentrates prepared from single units of whole blood and anticoagulated with CPDA-1 bind less anti-CD42b and more anti-CD62 than do platelets obtained by apheresis. These differences may be attributed to platelet sedimentation and the transient exposure of some of the platelets in the blood that is first collected during whole-blood donation to high concentrations of anticoagulant.

Adenine↗

PubMed1999

Corrected count increment and percent platelet recovery as measures of posttransfusion platelet response: problems and a solution.

BACKGROUND: Corrected count increment (CCI) and percent platelet recovery (PPR) are measures of response to platelet transfusion that "correct" the count increment for blood volume and number of platelets transfused. Their potential for data distortion is described, and a regression analysis is suggested that is more informative and avoids the inherent problems associated with using ratios as outcome measures. STUDY DESIGN AND METHODS: Data from the first platelet transfusion for 585 patients from the Trial to Reduce Alloimmunization to Platelets (TRAP) were used to model methods of analyzing posttransfusion platelet response. RESULTS: By linear regression analysis, unfiltered platelet components gave a greater posttransfusion increment on average (p = 0.001), but filtered platelets gave a greater increment per platelet transfused (p = 0.003). In contrast, CCI and PPR showed no difference between filtered and unfiltered platelets (p = 0.36 and p = 0.29, respectively) because they combined the effects of dose, filtration, and patient size. Slightly fewer patients are required for a study analyzed by regression analysis. CONCLUSION: Regression analysis of posttransfusion platelet increments should be used instead of CCI or PPR to compare the efficacy of platelet components. CCI and PPR should not be used to define platelet refractoriness as a study outcome, because these measures are biased in favor of platelet preparation techniques that provide fewer platelets.

Blood Platelets↗

PubMed2003

Effects of plumbagin on platelet aggregation and platelet-neutrophil interactions.

The effects of plumbagin were investigated on platelet aggregation in vitro and ex vivo, on the binding of thrombin-stimulated platelets to neutrophils, and platelet aggregation induced by intact neutrophils and N-formyl-methionyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF) activated neutrophils, by use of the methods of Hamburger, McEver and Born, respectively. The results showed that plumbagin in vitro significantly inhibited adenosine diphosphate (ADP)-, arachidonic acid (AA)-, or platelet activating factor (PAF)-induced platelet aggregation, in a concentration-dependent manner. The medium inhibitory concentrations (IC 50 ) were 39.4, 82.7 and 38.1 microM, respectively. Intragastric plumbagin at 10 mg/kg markedly suppressed platelet aggregation induced by ADP, AA, or PAF. Plumbagin decreased the binding between thrombin-stimulated platelets and neutrophils with an IC 50 of 62.9 microM. Plumbagin significantly inhibited washed platelet aggregation stimulated by fMLP- or PAF-activated neutrophils. The IC 50 values were 54.3 and 47.6 microM, respectively. On the other hand, plumbagin and aspirin increased the inhibition of intact neutrophils on AA-induced platelet aggregation. It is suggested that plumbagin inhibited platelet aggregation in vitro and ex vivo, suppressed the binding of activated platelets to neutrophils, inhibited platelet aggregation induced by activated neutrophils, and increased inhibition of intact neutrophils on platelet reactivity. Abbreviations. DMSO:dimethyl sulphoxide fMLP: N-formyl-methionyl-leucyl-phenylalanine ADP:adenosine diphosphate AA:arachidonic acid PAF:platelet activating factor

Adenosine Diphosphate↗

PubMed1994

Frozen platelet plates for platelet antibody detection and cross-match.

We performed 2 studies aimed at developing a frozen platelet panel suitable for platelet cross-matching. The stability of the most important platelet membrane glycoproteins and the reactivity of antigens of the human platelet antigen (HPA) and of the human leukocyte antigen (HLA) systems were evaluated with the platelet suspension immunofluorescence test (PSIFT) in a panel of platelets frozen in microplates with 6% dimethylsulfoxide. In study No. 1 we evaluated platelet reaction with a broad-spectrum weak anti-HLA and a potent anti-HPA-1a antiserum and the expression of glycoproteins Ib and IIb/IIIa complex on platelet membrane before freezing and after 0.5, 1, 2, 3, 4, 5, 6 and 12 months of storage at -80 degrees C. In study No. 2 we examined platelet reactivity with anti-HPA-1b, -HPA-2a, -HPA-3a, -HLA-A2, -HLA-A3 of platelets stored frozen for 12 months in parallel with fresh platelets from the same donors. Study No. 1 showed that glycoprotein expression was stable and that the weak anti-HLA and the potent anti-HPA-1a antibodies were clearly detected during 12 months at -80 degrees C. Of the 35 paired PSIFT performed in study No. 2 with fresh and frozen/thawed platelets incubated with anti-HPA-1b, -HPA-2a, -HPA-3a, -HLA-A2, -HLA-A3 antisera and AB serum, concordant reactions were obtained in all cases with the exception of 1 case of HLA-A3-positive platelets incubated with anti-HLA-A3 antiserum, that was reactive with frozen/thawed platelets but nonreactive with fresh platelets from the same donor.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Human Platelet↗

PubMed2004

Correlation between the extent of platelet activation in platelet concentrates and in vitro and in vivo parameters.

BACKGROUND AND OBJECTIVES: Platelet activation, which is necessary to stop bleeding, also occurs in vitro during the storage of platelet concentrates (PCs). However, it is unknown whether in vitro-activated platelets are able to reduce blood loss in the patient. We studied correlations between platelet activation in PCs and in vitro parameters (pH, platelet count, swirling effect, storage time). In addition, we studied the correlation between platelet activation and in vivo parameters [the volume of thorax drain fluid as a measure of blood loss, platelet count, international normalized ratio (INR), and activated partial thrombin time (APTT)] in a clinical pilot study. MATERIALS AND METHODS: White blood cell-reduced PCs prepared from five buffy coats and one plasma unit (n = 55; storage time: median, 5 days; range, 2-12 days) were sampled. Platelet activation (CD62p, CD63, CD42b), as measured by flow cytometry, pH, platelet count, swirling effect and storage time, was determined. For the in vivo pilot study, PCs (n = 21) stored for 2-7 days were also checked for the above parameters and transfused into patients (n = 21) immediately after coronary artery bypass graft surgery. The volume of thorax drain fluid was measured for up to 12 h after surgery, and the platelet count, INR and APTT were measured < 1 h and 16-24 h postsurgery. RESULTS: A good correlation (r2 > 0.5) was observed between CD62p and CD63, between CD62p and CD42b, between CD62p or CD63 and pH and between CD62p or CD63 and swirling effect. Also, a significant increase in platelet activation was observed for PCs stored for > or = 8 days (mean +/- standard deviation: CD62p, 41.6 +/- 30.7; CD63, 23.8 +/- 18.6), compared to PCs stored for 2-7 days (mean +/- standard deviation: CD62p, 12.3 +/- 4.8; CD63, 10.4 +/- 3.6). No correlation (r2 < or = 0.1) was observed between platelet activation and the in vivo parameters. CONCLUSIONS: Although a correlation between platelet activation and in vitro parameters was observed, no correlation was found between platelet activation and in vivo parameters. Possible explanations for this are a too low variance in platelet activation in transfused PCs, and too small a number of patients.

Antigens, CD↗

PubMed1994

Increased release of platelet-derived growth factor from platelets in chronic liver disease.

The concentrations of platelet-derived growth factor in serum in 7 healthy controls (61 +/- 9 years; mean +/- SD) and 10 patients (62 +/- 8 years) with chronic liver disease (chronic hepatitis and/or liver cirrhosis) were compared. The plasma concentration of platelet-derived growth factor was below the detection limit (< 0.45 microgram/l) in all the subjects studied. The peripheral blood platelet count in patients with chronic liver disease was significantly lower than that in control subjects. However, the concentration of platelet-derived growth factor in serum, which was assumed to be released from platelet, was similar in patients with chronic liver disease and control subjects. These results indicate that the mean amount of platelet-derived growth factor released from the same number (10(9)) of platelets, calculated from the serum platelet-derived growth factor concentration and the peripheral blood platelet count, in patients with chronic liver disease (33 +/- 11 ng/10(9) platelets) was significantly (p < 0.01) higher than that in control subjects (14 +/- 5 ng/10(9) platelets). Moreover, the amount of platelet-derived growth factor released from 10(9) platelets inversely correlated with the serum concentration of pseudocholinesterase activity (r = -0.65, p < 0.01), and correlated positively (r = 0.91, p < 0.01) with the percent retention of indocyanine green in serum, in all subjects studied. These findings suggest that the amount of platelet-derived growth factor releasable from platelets of patients with chronic liver disease is higher than that in normal subjects and that it correlates with the severity of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2003

Evaluation of platelet storage lesions in platelet concentrates stored for seven days.

BACKGROUND & OBJECTIVES: Platelet storage lesions (PSL) are detrimental to the post transfusion functional capacity of platelets. As EDTA enhances the storage-induced changes, changes in platelet indices with and without EDTA incubation are promising new tests to monitor the PSL. The present study was undertaken to monitor the PSL in 40 units of pooled platelet concentrates harvested by platelet rich plasma (PRP) method and stored for seven days in second generation platelet storage containers using conventional in vitro tests and platelet indices. METHODS: Morphological changes in platelets were monitored by automated haematological cell counter for platelet count and mean platelet volume (MPV). Samples were incubated with K2EDTA for 1 h and platelet indices were repeated on the EDTA incubated samples. Difference between pre-and post-EDTA incubation of platelet count (dPLT) and MPV (dMPV) were calculated. Metabolic parameters such as pH, pO2, pCO2 and ATP were measured. RESULTS: There was no significant change in the indices without EDTA during storage, however, after EDTA incubation, significant changes were noted in dPLT and dMPV. The mean dPLT on day 0 was 75.15 x 10(3)/microl decreasing to 44.4 x 10(3)/microl on day 7, while dMPV from 0.76 fl on day 0 increased to 1.34 fl on day 7 (P < 0.05). Metabolic parameters showed a significant decrease in pH and pCO2 concurrent with increasing pO2 during storage (P < 0.05). Average ATP level on day 0 was 21.09 micromol/dl falling to 10.59 micromol/dl on day 7. INTERPRETATION & CONCLUSION: The results indicate that storage induced lesions take place even in second generation platelet storage containers under recommended conditions of storage. Platelet indices especially after EDTA incubation are useful in monitoring PSL. However, how much these changes contribute to poor post transfusion survival and haemostatic function of platelets need to be investigated.

Adenosine Triphosphate↗

PubMed1987

Free platelet count and size distribution during C1q inhibition of collagen-induced platelet aggregation.

Electronic free platelet counting was more sensitive than turbidimetry to detect collagen-induced platelet activation in human platelet-rich plasma. Purified human C1q exhibited a greater inhibitory effect on collagen-induced platelet aggregation in turbidimetry than free platelet counting. Because the change from small to large platelet aggregates is responsible for the continuing increase in light transmission, C1q was likely more capable of blocking the formation of large platelet aggregates than the formation of small aggregates from single platelets. The rate of change by collagen in light transmission and free platelet count was reduced in the presence of C1q but the timing of the peak response remained the same. Electronic platelet sizing revealed that the volume of single platelets transiently increased during the turbidimetric "lag phase". The mean, mode and median volume of the remaining free platelets then decreased, suggesting a selective loss of large, functionally more active platelets and/or platelet degranulation. C1q had no effect on the volume increment during the "lag phase", but reduced the subsequent fall in the volume of free platelets.

Adult↗

PubMed1996

An autosomal dominant, qualitative platelet disorder associated with multimerin deficiency, abnormalities in platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen and an epinephrine aggregation defect.

Multimerin is a massive soluble, multimeric protein found in platelets and endothelial cells. Recent studies identified multimerin as a specific coagulation factor V binding protein, complexed with platelet, but not plasma, factor V. These findings led us to investigate individuals with inherited factor V deficiencies for possible multimerin abnormalities. Platelet proteins were evaluated using immunoassays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, immunoprecipitation, and direct binding studies. Patients with factor V Quebec, a disorder with abnormal platelet factor V, had a quantitative deficiency in multimerin (n = 11 tested; mean, 12.5%; range, 5% to 27% of the normal pool; normal range, 45% to 214%) with a normal multimer pattern. Quantitative and qualitative abnormalities were detected in their platelet factor V. An unrelated patient who was deficient in platelet and plasma factor V had normal platelet multimerin. The levels of platelet beta-thromboglobulin, von Willebrand factor, thrombospondin, and fibrinogen antigen were normal in the factor V Quebec patients. However, proteins with abnormal mobility were detected in their platelet lysate and releasate, and their platelet thrombospondin, von Willebrand factor, and fibrinogen showed evidence of proteolytic degradation. Platelet counts of the factor V Quebec patients ranged from mildly thrombocytopenic to low normal (mean, 159 x 10(9)/L; range, 104 to 198 x 10(9)/L). In addition, their platelets failed to aggregate in response to 6 to 10 micromol/L epinephrine despite normal numbers of platelet alpha 2-adrenergic receptors. These data indicate that patients with factor V Quebec have an inherited bleeding disorder distinct from other platelet disorders and associated with multiple abnormalities, including multimerin deficiency, abnormal platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen, and an epinephrine aggregation defect.

Afibrinogenemia↗

PubMed1991

Effects of platelet activating factor on rat platelets in vivo.

Platelet activating factor (PAF) is not able to aggregate rat platelets in vitro. Due to the agonist effects of PAF on multiple cells, a possible role of PAF in the activation of rat platelets in vivo where different cells may influence each other was investigated. The pulmonary microembolization of 51Cr-labelled activated platelets was used as in vivo model. This model allowed us to monitor platelet behaviour by means of non-invasive methods. In contrast to results obtained in vitro, PAF activated rat platelets in vivo. The pulmonary microembolization of the platelets was dose-dependent and rapidly reversible. About 0.5 microgram/kg PAF caused a half-maximal rise of platelet-bound radioactivity in the thorax. Activation of the platelets by PAF was followed by extreme desensitization, so that a second injection of PAF did not provoke a significant response of the platelets. Platelet function was, however, not completely impaired because they still accumulated in the thorax after the application of ADP (50 micrograms/kg). That pulmonary entrapment had taken place was shown by a 3-fold increase in lung specific radioactivity. This was accompanied by a short-lasting thrombocytopenia. The PAF antagonist, WEB 2170 (30 micrograms/kg), significantly inhibited the microembolization of the platelets induced by PAF. Under in vitro conditions leukocytes purified from rat blood and activated by PAF were able to induce platelet aggregation. These results demonstrate that a PAF-specific activation of rat platelets is achievable in vivo which is probably mediated by other cells.

Adenosine Diphosphate↗

PubMed1998

Hemocompatibility of treated polystyrene substrates: contact activation, platelet adhesion, and procoagulant activity of adherent platelets.

Platelet adhesion to biomaterials is often used as an index of blood compatibility, but a more clinically relevant issue is whether the adherent platelets are able to promote clot formation (i.e., if they are in the procoagulant state). Platelets rapidly generate thrombin when they are in the procoagulant state and the VA/Xa complex is present. We found that adherent platelets are procoagulant by three different methods: binding of FITC-Annexin V, acceleration of thrombin generation in the presence of Xa, Va, and prothrombin; and clotting of recalcified plasma. In the clotting times studies, the effect of adherent platelets on TCPS was completely eliminated by the addition of Annexin V, which is known to bind tightly to procoagulant platelets. The degree of procoagulant activity of adherent platelets was determined by measuring thrombin generation rates in the presence of the clotting factors Va, Xa, and prothrombin and normalizing to the number of adherent platelets. Two key observations were made in these studies. First, the procoagulant activity of platelets adherent to untreated and to several types of treated polystyrenes, as well as to glass and PET, was much greater than the procoagulant activity of unstimulated bulk phase platelets. Little difference in the procoagulant activity of adherent platelets was observed among the materials tested, however. Second, the procoagulant activity of platelets prestimulated with ionophore and subsequently allowed to adhere to Plastek M was much greater than when adherent platelets were stimulated by the adhesion event only. Measured values for platelet adhesion, platelet activation, and contact activation of blood plasma are discussed in the context of their potential combined impact on blood clotting.

Annexin A5↗

PubMed2005

The platelet receptor for type III collagen (TIIICBP) is present in platelet membrane lipid microdomains (rafts).

Platelet interactions with collagen are orchestrated by the presence or the migration of platelet receptor(s) for collagen into lipid rafts, which are specialized lipid microdomains from the platelet plasma membrane enriched in signalling proteins. Electron microscopy shows that in resting platelets, TIIICBP, a receptor specific for type III collagen, is present on the platelet membrane and associated with the open canalicular system, and redistributes to the platelet membrane upon platelet activation. After platelet lysis by 1% Triton X-100 and the separation of lipid rafts on a discontinuous sucrose gradient, TIIICBP is recovered in lipid raft-containing fractions and Triton X-100 insoluble fractions enriched in cytoskeleton proteins. Platelet aggregation, induced by type III collagen, was inhibited after disruption of the lipid rafts by cholesterol depletion, whereas platelet adhesion under static conditions did not require lipid raft integrity. These results indicate that TIIICBP, a platelet receptor involved in platelet interaction with type III collagen, is localized within platelet lipid rafts where it could interact with other platelet receptors for collagen (GP VI and alpha2beta1 integrin) for efficient platelet activation.

Blood Platelets↗

PubMed1983

The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration.

Bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration were measured in rabbits recovering from thrombocytopenia caused by a single injection of anti-platelet serum. Similar measurements were made on rabbits in a steady state of normal platelet production. The effects of a sustained state of thrombocytopenia on megakaryocyte DNA concentration were investigated by repeated daily injections of anti-platelet serum. It is shown that bleeding time depends on both platelet count and mean platelet volume. Furthermore changes in mean platelet volume appear to play a more important role in haemostasis than changes in platelet count. The mean megakaryocyte nuclear DNA concentration is significantly increased after 24 hours of thrombocytopenia and continues to increase as thrombocytopenia is sustained. Thromboxane B2 production/unit volume of platelet is increased in platelets produced after 24 hours of thrombocytopenia compared with platelets produced in normal steady state function. As a consequence platelets produced in response to thrombocytopenia not only have a larger mean platelet volume but are also more reactive. Mean platelet volume, as well as platelet count, should be considered as an index of haemostasis and its dysfunction, thrombosis.

Animals↗

PubMed2003

Randomized comparison of platelet-leukocyte aggregates and platelet activation in blood: heparin-coated coiled wire stent implantation versus balloon angioplasty in acute myocardial infarction.

INTRODUCTION: Stent implantation has been shown to be superior to balloon angioplasty in patients with acute myocardial infarction (AMI). Newer trials indicate that platelet-leukocyte aggregates are a more sensitive marker for platelet activation than platelet surface marker. Our study examined platelet activation and platelet-leukocyte interaction in blood in patients with AMI randomized to heparin-coated stent implantation versus balloon angioplasty. MATERIALS AND METHODS: Forty-seven patients with AMI were included into our study. Patients were randomized to heparin-coated stent implantation (n=31) or balloon angioplasty (n=16). Platelet activation, total platelet-leukocyte aggregates and aggregate composition in blood were assessed by flow cytometry before, immediately after and 24 h after intervention. RESULTS: No differences in platelet activation, total platelet-leukocyte aggregates and aggregate composition were found between both groups before intervention. Immediately after intervention, platelet activation was comparably increased in both groups. Patients treated with heparin-coated stent showed a decrease in total platelet-leukocyte aggregates 24 h after intervention (3.9% [2.8; 4.7] versus 3.2% [2.4; 4.1]; p<0.01). Platelet-monocyte conjugates decreased 24 h after heparin-coated stent implantation compared to balloon angioplasty alone (0.28% [0.17; 0.42] versus 0.49% [0.45; 0.79]; p<0.05). No difference in total platelet-leukocyte aggregates was found in patients treated with balloon angioplasty alone. CONCLUSIONS: An inhibitory effect of heparin-coated stent implantation on total platelet-leukocyte aggregates and platelet-monocyte conjugates in blood was demonstrated in patients with AMI. This reflects heparin-coated stent implantation to be less thrombogenic than balloon angioplasty alone.

Aged↗

PubMed2002

Markers of platelet activation and platelet-leukocyte interaction in patients with myeloproliferative syndromes.

INTRODUCTION: Changes in platelet count and function contribute to thrombo-hemorrhagic episodes in chronic myeloproliferative syndromes (MPS). We used flow cytometry to study platelet-leukocyte conjugates and markers of platelet activation in patients with MPS. METHODS: Whole blood from patients with chronic myelogenous leukemia (CML), polycythemia vera (PV), chronic myelofibrosis (MF), and essential thrombocythemia (ET) and from healthy volunteers was prepared for flow cytometry. Platelet microparticles and platelet microaggregates were identified with anti-CD42b and forward scatter, activated platelets with anti-CD62p. Anti-CD42b, anti-CD14, and anti-CD45 were used to study platelet-leukocyte conjugates. RESULTS: The percentage of CD62p-positive platelets was elevated in all myeloproliferate syndrome subtypes. The median percentage of platelet microparticles was 5.2% in controls and significantly higher in PV (12.0%), MF (11.0%), and ET (11.0%, all p<0.05). There was an increased percentage of platelet-neutrophil conjugates in patients with PV (8.3%) and ET (10.4%) compared to normal controls (6.8%, all p<0.05). Platelet-monocyte conjugates were 8.0% in controls and elevated in PV (15.4%) and ET (15.0%, all p<0.05). Patients with a history of venous or arterial thrombotic events had slightly less platelet-leukocyte conjugates and slightly more microparticles than patients without thrombosis; however, this difference was not statistically significant. CONCLUSIONS: These findings suggest that platelet-leukocyte conjugate formation occurs in myeloproliferative syndromes and indicates platelet activation. Also, platelet microparticles are elevated and might provide a catalytic surface for thrombin generation. This could explain the clinical observation that patients with myeloproliferative syndromes have an increased risk to experience arterial or venous thrombotic events.

Adult↗

PubMed2003

Platelet-mediated microvascular inflammation and thrombosis in thrombocythemia vera: a distinct aspirin-responsive arterial thrombophilia, which transforms into a bleeding diathesis at increasing platelet counts.

Erythromelalgia is the main, pathognomonic and presenting symptom in patients with essential thrombocythemia and thrombocythemia associated with polycythemia vera. Complete relief from erythromelalgic and acrocyanotic pain is obtained with the cyclooxygenase inhibitors aspirin and indomethacin, but not with sodiumsalicylate, dipyridamol, sulfinpyrozone and ticlopedine. Thus, cyclooxygenase metabolites are necessary for erythromelalgia to develop. Local platelet consumption in erythromelalgic areas became evident by the demonstration of arteriolar fibromuscular intimal proliferation and occlusions by platelet-rich thrombi in skin biopsies, by the findings of shortened platelet survival times, significant higher levels of platelet activation markers beta-thromboglobulin, thrombomoduline and increased urinary thromboxane B2 excretion in thrombocythemia patients suffering from erythromelalgia. Aspirin treatment of erythromelalgia in thrombocythemia patients resulted in the disappearance of the erythromelalgic, thrombotic signs and symptoms, correction of the shortened platelet survival times, and a significant reduction of the increased levels of beta-TG, PF4, TM and urinary TxB2 excretion to normal. Erythromelalgia is frequently preceded or followed by atypical transient neurologic, ocular or coronary ischemic symptoms, which specifically respond to low-dose aspirin or reduction of platelet counts to normal. The broad spectrum of acropareshesias, erythromelalgia and acrocyanotic ischemia together with the episodic and transient atypical TIAs and ocular or coronary ischemic symptoms are caused by spontaneous activation and aggregation of hypersensitive platelets in the end-arterial microvasculature involving the peripheral, cerebral and coronary circulation of thrombocythemia patients. These microvascular circulation ischemic disturbances in thrombocythemia vera already occur at platelet counts in excess of 400 x 10(9) l(-1). Low-dose aspirin is highly effective and safe in the cure and prevention of thrombotic and ischemic events and does not elicit bleedings at platelet counts below 1000 x 10(9) l(-1). Spontaneous hemorrhages usually occur at very high platelet counts far in excess of 1000 x 10(9) l(-1) (HT) due to an acquired von Willebrand factor deficiency at increasing platelet counts. At platelet counts between 1000 and 2000 x 10(9) l(-1), thrombosis and bleeding (ETT and HT) frequently occur in sequence or paradoxically and low-dose aspirin does prevent thrombotic complications but aggravates or may elicit bleeding symptoms. Reduction of the platelet count to below 1000 x 10(9) l(-1) by platelet lowering agents usually results in the disappearance of the bleeding tendency and improvement of the von Willebrand syndrome, but the thrombotic tendency persists as long as platelet counts are above the upper limit of normal.

Aspirin↗

PubMed1991

Alboaggregin-B: a new platelet agonist that binds to platelet membrane glycoprotein Ib.

A new protein, called alboaggregin-B (AL-B), has been isolated from Trimeresurus albolabris venom by ion-exchange chromatography. It agglutinated platelets without the need for Ca2+ or any other cofactor. The purified protein showed an apparent molecular mass on SDS-PAGE and gel filtration of about 23 kDa under nonreducing conditions. Ristocetin did not alter the binding of AL-B to platelets or affect AL-B-induced platelet agglutination. Agglutinating activity was not dependent on either proteolytic or lectin-like activity in AL-B. Binding analysis showed that AL-B bound to platelets with high affinity (Kd = 13.6 +/- 9.3 nM) at approximately 30,800 +/- 14,300 binding sites per platelet. AL-B inhibited the binding of labeled bovine von Willebrand factor (vWF) to platelets. Monoclonal antibodies against the 45-kDa N-terminal domain of platelet glycoprotein Ib inhibited the binding both of AL-B and of bovine vWF to platelets, and also inhibited platelet agglutination induced by AL-B and bovine vWF. Specific removal of the N-terminal domain of GPIb by treatment of the platelets with elastase or Serratia marcescens protease reduced the binding of labeled AL-B and bovine vWF to platelets and blocked platelet agglutination caused by both agonists. Monoclonal antibodies to glycoprotein IIb/IIIa, to bovine vWF, and to bovine serum albumin did not show any effect on the binding of AL-B to platelets. Our results indicate that the binding domain for AL-B on platelet GPIb is close to or identical with the one for vWF. This new protein may be a very useful tool for studying the interaction between platelets and vWF.

Antibodies, Monoclonal↗

PubMed2000

Generation of annexin V-positive platelets and shedding of microparticles with stimulus-dependent procoagulant activity during storage of platelets at 4 degrees C.

BACKGROUND: The ability of propyl gallate to activate platelet factor 3 has been determined through the activated partial thromboplastin time, but its effect on phosphatidylserine has not been established. STUDY DESIGN AND METHODS: A novel platelet activator, propyl gallate, was introduced to a study of platelets stored at 4 degrees C. The effects of storage on platelet coagulation activity, on phosphatidylserine, and on the shedding of activated and activable membrane particles (microparticles) were examined by activated plasma clotting time, and the effect on annexin V binding was examined by gated flow cytometry. The ratios of annexin V binding and microparticle shedding in stored platelet samples were compared with those in fresh platelets stimulated with propyl gallate. RESULTS: Microparticle shedding by stored platelets compensated for the diminished procoagulant potential of intact platelets (shown as the total propyl gallate-dependent platelet factor 3 activity), which did not change during prolonged (20-day) storage, but levels of phosphatidylserine confined to microparticles increased dramatically as platelet counts fell. Both annexin V binding and microparticle shedding increased spontaneously with storage and artificially with propyl gallate stimulation. However, at the same level of annexin V binding, stored platelets shed more microparticles than did fresh platelets stimulated with propyl gallate. CONCLUSION: Propyl gallate induces platelet procoagulant activity and annexin V binding. Stored platelets differ from fresh platelets in a lower reactivity to propyl gallate activation and a higher rate of microparticle shedding.

Adult↗