The Role of Platelets in the Pathogenesis of Thrombosis and Hemorrhage in Patients with Thrombocytosis

1977 ◽  
Vol 38 (04) ◽  
pp. 1085-1096 ◽  
Author(s):  
Peter N. Walsh ◽  
Scott Murphy ◽  
William E. Barry
Keyword(s):  
Platelet Function ◽  
Bleeding Complications ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Coagulant Activity ◽  
Hemorrhagic Complications ◽  
Myeloproliferative Diseases ◽  
Thrombotic Complications ◽  
Preliminary Study

SummarySome patients with thrombocytosis due to myeloproliferative diseases or other etiologies experience thromboembolic complications and others may bleed excessively. It seems unlikely that elevations in platelet count per se are a direct cause either of thrombosis or of hemorrhage. In an effort to ascertain whether variations in platelet function might determine whether an individual patient experiences thrombotic or hemorrhagic complications we have evaluated platelet function in 22patients with thrombocytosis due to a variety of etiologies. The results of platelet counts, bleeding time determinations, and studies of platelet aggregation were similar in patients with thrombosis, in patients with bleeding and in patients with neither complication. Therefore, detailed studies of platelet coagulant activities were carried out in 8patients. The results of platelet coagulant activity assays were normal in all 3patients with thrombocytosis and neither thrombotic nor bleeding complications and an additional 3patients with myeloproliferative diseases, normal platelet counts and no thrombohemorrhagic complications. In 2patients with thrombotic complications significant elevation of platelet coagulant activities concerned with the early phases of intrinsic coagulation were observed whereas in 2patients with severe hemorrhagic complications deficiences of either contact forming activity or collagen-induced coagulant activities were evident. This preliminary study suggests the possibility that variations in platelet coagulant activities concerned with the early stages of intrinsic coagulation may determine whether patients with thrombocytosis will experience bleeding or thrombotic complications.

Determination and Treatment of Disorders of Primary Haemostasis

1999 ◽  
Vol 19 (04) ◽  
pp. 168-175 ◽  
Author(s):  
M. Weippert-Kretschmer ◽  
V. Kretschmer
Keyword(s):  
Platelet Function ◽  
Bleeding Risk ◽  
Bleeding Complications ◽  
Bleeding Tendency ◽  
Platelet Counts ◽  
Platelet Function Disorders ◽  
Perioperative Bleeding ◽  
Before And After ◽  
Low Sensitivity

SummaryPerioperative bleeding complications due to disorders of primary haemostasis are often underestimated. Routine determination of primary haemostasis is still problematic. The in vivo bleeding time (BT) shows low sensitivity and high variability. In this contribution the results and experiences with the IVBT having been obtained in various studies and during 10 years of routine use are reported. Patients and Methods: Blood donors before and after ASA ingestion, patients with thrombocytopenia as well as congenital and acquired platelet function disorders. Monitoring of desmopressin efficacy. IVBT with Thrombostat 4000 (tests with CaCl2 = TST-CaCl2 and ADP = TST-ADP) and PFA-100 (test cartridges with epinephrine = PFA-EPI and ADP = PFA-ADP). Results and Conclusions: IVBT becomes abnormal with platelet counts <100,000/μl. With platelet counts <50,000/μl the results are mostly outside the methodical range. IVBT proved clearly superior to BT in von Willebrand syndrome (vWS). All 16 patients with vWS were detected by PFA-EPI, whereas with BT 7 of 10 patients with moderate and 1 of 6 patients with mild forms of vWS were spotted. The majority of acquired and congenital platelet function disorders with relevant bleeding tendency were detectable by IVBT. Sometimes diagnostic problems arose in case of storage pool defect. Four to 12 h after ingestion of a single dose of 100 mg ASA the TST-CaCl2 became abnormal in all cases, the PFA-EPI only in 80%. However, the ASA sensitivity of TST-CaCl2 proved even too high when looking for perioperative bleeding complications in an urological study. Therefore, the lower ASS sensitivity of the PFA-100 seems to be rather advantageous for the estimation of a real bleeding risk. The good efficacy of desmopressin in the majority of cases with mild thrombocytopenia, congenital and acquired platelet function disorders and even ASS-induced platelet dysfunction could be proven by means of the IVBT. Thus IVBT may help to increase the reliability of the therapy. However, the IVBT with the PFA-100 is not yet fully developed. Nevertheless, routine use can be recommended when special methodical guidelines are followed.

scholarly journals Thrombocytopenia in septicemia: the role of disseminated intravascular coagulation

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 88-92 ◽  
Author(s):  
PB Neame ◽  
JG Kelton ◽  
IR Walker ◽  
IO Stewart ◽  
HL Nossel ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Gel Chromatography ◽  
Severe Thrombocytopenia ◽  
Intravascular Coagulation ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Platelet Survival ◽  
Possible Cause

Abstract The mechanism of isolated thrombocytopenia in septicemia is unknown, but compensated disseminated intravascular coagulation (DIC) has been suggested as a possible cause. To investigate this possibility, platelet counts and sensitive assays for in vivo thrombin and plasmin generation, including fibrinogen gel chromatography and fibrinopeptide A (FPA) assays, were obtained on 31 septicemic patients. Fifteen of 17 patients with gram-negative septicemia and 8 of 14 patients with gram- positive septicemia had thrombocytopenia. Platelet survival studied demonstrated a decreased platelet survival. In 11 of 12 patients with severe thrombocytopenia (platelet count less than 50,000mul), there was laboratory evidence of intravascular coagulation. In contrast, there was little evidence of intravascular coagulation in 8 of 11 patients with moderate thrombocytopenia (platelet counts 50,000 to less than 150,000/mul) or in 7 of 8 patients with normal platelet counts. This report indicates that while DIC accompanies thrombocytopenia in many patients with severe thrombocytopenia, there is frequently little evidence for intravascular coagulation in patients with moderate thrombocytopenia. It is apparent that factors other than intravascular thrombin must play a role in producing the thrombocytopenia of septicemia.

Changes in Platelet Function and Platelet Counts During Substitution Therapy in Haemophiliacs and Produced by Plasmapheresis in Patients Suffering from Inhibitors

1979 ◽  
Author(s):  
E. Dumitrescu ◽  
I. Ambrus ◽  
Kh. Nienhaus ◽  
B. Podolsak ◽  
E. Wenzel
Keyword(s):  
Factor Viii ◽  
Platelet Function ◽  
Clinical Signs ◽  
Bleeding Complications ◽  
Substitution Therapy ◽  
Drug Induced ◽  
Platelet Counts ◽  
Before And After ◽  
Factor Viii Concentrates ◽  
Laboratory Investigations

We noticed a systematic increase in small platelets (evaluated by electronical analysis of platelet volune distribution, using the Coulter Counter equipment, Wenzel 1977) during substitution therapy in patients suffering from haemophilia (N = 60). Laboratory investigations on these patients were performed before substitution and then 30 min., 60 min., 120 min. and 24 hours after infusion of factor-VIII-concentrationa (Inmuno, Schwab, Behring, factor-VIII-concentrates 20 U/kg b.w.). The same investigations were performed before and after plasmapheresis using a Hemonetric cell separator (N = 7}. in 48 of the patients, the clinical signs were insignificant (bleeding time, according to Duke, was found to be normall, although the platelet changes ware considerable (decrease in platelet count and increase of the percentage of platelets smaller than 4.5 μ3). However, significant test results were noticed in a haemophiliac patient suffering from inhibitory- and drug-induced platelet disorders during and after plasmapheresis. We observed bleeding complications only in 2 cases (Duke; 7 min. and 9 min.). Yet, a coneiderable decrease in platelet counts was observed as well as a significant increase in the percentages of small platelets (4.5 μ3, N = 48) in all cases. Controlling platelet function in haemophiliacs following substitution therapy could be essential as well as controlling the usual hemolysis parameters after plasmapheresis.

Argatroban Associated Bleeding Complications.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1867-1867
Author(s):  
David Berz ◽  
Gerald A. Colvin ◽  
Priya Mital ◽  
Peter J. Quesenbery
Keyword(s):  
Multivariate Logistic Regression Analysis ◽  
Direct Thrombin Inhibitor ◽  
Bleeding Complications ◽  
Thrombin Inhibitor ◽  
Time Interval ◽  
Study Cohort ◽  
Transfusion Therapy ◽  
Major Hemorrhage ◽  
Hemorrhagic Complications ◽  
Thrombotic Complications

Abstract Background: Heparin induced thrombocytopenia (HIT) is a frequently observed side effect observed with heparin administration. Treatment for this condition includes direct thrombin inhibitor (DTI) therapy. Major hemorrhagic complications are considered rare events in this setting. Methods: This is a case series of patients diagnosed with HIT in a tertiary medical referral center. The diagnosis of HIT was established on the base of clinical criteria. All included patients had positive HIT ELISA based antibody testing during the time interval from July 2006 to July 2007 and all patients were treated with argatroban. A systematic review for hemorrhagic and thrombotic complications of argatroban therapy was performed. Major hemorrhage was defined as clinically identified bleeding with the demand for transfusion therapy. Thrombotic complications were defined as thrombosis evidenced by imaging studies developing during argatorban therapy. We performed bivariate and multivariate logistic regression analysis to identify demographic and clinical factors that influence the development of complications of argatroban therapy as treatment for HIT. Examined covariates were gender, age, type of service the patient was admitted under (surgical versus medical), amount of comorbidities, preexisting history of gastrointestinal bleeding, documented thrombotic or thrombembolic event at the time point of HIT diagnosis and coexisting coexisting coagulopathy other than HIT. Results: We identified 102 patients with the diagnosis of HIT. The median optical density (OD) of the ELISA HIT immunoassay was 1.23 (95% CI 0.93–1.43). We identified 11 (10.7%) major hemorrhagic events in patients on argatroban. Four patients (3.9%) died as a consequence of major hemorrhagic complications. No thrombotic events were identified in our study cohort. As statistically significant; predictors for clinically relevant hemorrhagic complications in our model remained male gender, preexisting GI bleeding history and being patient on a surgical service. Conclusion: The incidence of major hemorrhagic episodes with agatroban therapy is significantly higher then generally reported and the mortality rate is very disturbing. These data suggest that alternatives to standard direct thrombin inhibitor therapy should be aggressively pursued.

SHPing in different directions in platelet production

Blood ◽  
2013 ◽  
Vol 121 (20) ◽  
pp. 4018-4019 ◽  
Author(s):  
Jorge Di Paola
Keyword(s):  
Platelet Function ◽  
Conditional Knockout ◽  
Murine Models ◽  
Platelet Production ◽  
Platelet Counts

In this issue of Blood, Mazharian and colleagues characterize Shp1 and Shp2 conditional knockout (KO) murine models, underscoring the role of these phosphatases not only on platelet function but also on megakaryocyte development and platelet counts and size.1

Post-DDAVP Thrombocytopenia in Type 2B von Willebrand Disease Is not Associated with Platelet Consumption: Failure to Demonstrate Glycocalicin Increase or Platelet Activation

1999 ◽  
Vol 81 (02) ◽  
pp. 224-228 ◽  
Author(s):  
A. Steffan ◽  
E. Pontara ◽  
A. Zucchetto ◽  
C. Rossi ◽  
L. De Marco ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Surface Expression ◽  
Von Willebrand Disease ◽  
Platelet Surface ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Thrombotic Complications ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThrombocytopenia is frequently reported in type 2B von Willebrand disease (vWD), and thought to be related to the abnormally high affinity of 2B von Willebrand factor (vWF) for platelet GPIb-IX. To gain an insight into the nature of this thrombocytopenia, we measured plasma glycocalicin (GC) levels (as a marker of platelet turnover), and platelet surface expression of the alpha granule protein P-selectin (as a marker of platelet activation) in 9 patients with type 2B vWD before, and in 4 patients also following the infusion of 1-desamino-8-d-arginine vasopressin (DDAVP). Three patients presented a persistent decrease of platelet counts in the resting condition. GC levels were within the normal range, regardless of the platelet counts, in all but one patient who presented, on the other hand, a normal platelet count. Moreover, platelets expressed normal amounts of P-selectin on their surface, regardless of platelet counts. These findings suggest that the thrombocytopenia observed in type 2B vWD is not due to platelet activation and subsequent consumption in circulation.Despite a significant, albeit transient, decrease in platelet count, DDAVP did not induce an increase in plasma GC levels, nor enhance P-selectin expression. These observations indicate that the acute post-DDAVP thrombocytopenia in type 2B vWD is not related to platelet activation and consumption. We advance that the post-DDAVP 2B vWF is hemostatically more active, and able to induce agglutination but not aggregation of circulating platelets. This would explain both the prompt recovery of basal platelet counts after the post-DDAVP decrease, and the lack of reported thrombotic complications in this disorder.Therefore, even though 2B vWF is characterized by an enhanced affinity for the platelet surface, its binding to platelet GPIb-IX in the soluble phase is not able to induce true platelet aggregation; vWF thus appears to be mainly an adhesive protein, rather than an aggregating agent.

scholarly journals Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1684-1691 ◽  
Author(s):  
SB Lee ◽  
AK Rao ◽  
KH Lee ◽  
X Yang ◽  
YS Bae ◽  
...  
Keyword(s):  
Phospholipase C ◽  
G Protein ◽  
Platelet Function ◽  
High Performance ◽  
Immunoblot Analysis ◽  
Human Platelets ◽  
Normal Platelet ◽  
Beta 2 ◽  
First Time

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.

scholarly journals Cerebellar infarct with neurogenic pulmonary edema following viper bite

2012 ◽  
Vol 03 (01) ◽  
pp. 74-76 ◽  
Author(s):  
Salil Gupta ◽  
A.K. Tewari ◽  
Velu Nair
Keyword(s):  
Mechanical Ventilation ◽  
Pulmonary Edema ◽  
Snake Venom ◽  
Bleeding Complications ◽  
Neurogenic Pulmonary Edema ◽  
Ventricular Drainage ◽  
Good Recovery ◽  
Hemorrhagic Complications ◽  
Thrombotic Complications ◽  
Cerebellar Infarct

ABSTRACTRussell′s viper (Daboia russelli) bites are well known to cause bleeding complications. However, thrombotic complications are rare. We present the case details of a female who was bitten by a Russell′s viper (Daboia russelli) in her village. She then developed features of envenomation in the form of hemorrhagic episodes. She received 27 vials of polyvalent anti-snake venom to which the hemorrhagic complications responded. After about 48 h of the bite she developed features of cerebellar infarct along with pulmonary edema which was in all probability neurogenic in origin. She was managed with mechanical ventilation and extra ventricular drainage with good recovery. We discuss the likely pathogenesis of the infarct and pulmonary edema occurring in a patient with viper bite and other features of envenomation.

scholarly journals Clinical and Experimental Studies on the Bleeding Tendency During Defibrinogenation Therapy

1977 ◽  
Author(s):  
S. Ishimaru ◽  
K. Furukawa ◽  
M. Takahashi ◽  
M. Fujimaki ◽  
K. Fukutake
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Surgical Procedure ◽  
Postoperative Bleeding ◽  
Experimental Studies ◽  
Bleeding Complications ◽  
Fibrinogen Concentration ◽  
Bleeding Tendency ◽  
Normal Platelet ◽  
Normal Limits

Defibrinogenation with thrombin-like enzyme is expected to be a new type of anticoagulant therapy without serious bleeding complications. However, it appears to be dangerous to perform surgical procedure in defibrinogenated state. In order to investigate the causes of the bleeding tendency which occurs during defibrinogenation therapy, the following clinical and experimental studies were undertaken. Ten mongrel dogs were used, the superior caval vein was replaced by expanded polytetrafluoroethylene graft. 50 to 100 μl/kg of batroxobin was administered 2 days prior to the operation. 5 out of 10 dogs died due to bleeding postoperativelly, and the causes of the bleeding seemed to be the decreased fibrinogen concentration and the reduced platelet function. Fifteen patients suffering from peripheral vascular thrombosis were treated with 30 to 60 μl/kg of batroxobin. In 9 patients, urokinase was administered combined with batroxobin. No bleeding complications were observed in these patients. In another 6 patients, surgical procedure was performed after batroxobin administration. Postoperative bleeding was observed in one out of these 6 patients. This patient was operated on after the initial administration of batroxobin. FDP level was 512 μg/ml and ADP induced platelet aggregation was within normal limits, but fibrinogen concentration was unmeasurable at the time of operation. The cause of the bleeding seemed to be the decreased fibrinogen concentration. From these clinical experiences, it is suggested that platelet adhesion to glass and ADP induced platelet aggregation are not influenced by the decreased fibrinogen concentration nor the increased level of FDP during the defibrinogenation therapy with batroxobin. These results indicate that an adequate level of fibrinogen is needed for certain hemostasis besides normal platelet function.

scholarly journals Correlation of Thrombosis With Increased Platelet Turnover in Thrombocytosis

Blood ◽  
1998 ◽  
Vol 91 (4) ◽  
pp. 1288-1294 ◽  
Author(s):  
Henry M. Rinder ◽  
Judith E. Schuster ◽  
Christine S. Rinder ◽  
Chao Wang ◽  
Helen J. Schweidler ◽  
...  
Keyword(s):  
Platelet Count ◽  
Treatment Response ◽  
Myeloproliferative Disorders ◽  
Healthy Controls ◽  
Thrombotic Risk ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Reticulated Platelets ◽  
Thrombotic Complications ◽  
Deep Vein

Abstract There are no readily applicable methods to routinely assess thrombosis risk and treatment response in thrombocytosis. Reticulated platelets (RP) define the most recently released platelets in the circulation, and the RP% has been shown to estimate platelet turnover in thrombocytopenic states. We examined whether increased RP values were associated with thrombotic complications in thrombocytosis. Platelet count, RP%, and absolute RP count were measured at presentation in 83 patients with chronic or transient thrombocytosis, 46 patients with deep vein (DVT) or arterial (ART) thrombosis and normal platelet counts, and 83 healthy controls with normal platelet counts. Chronic thrombocytosis patients presenting with thrombosis (n = 14) had significantly higher RP% (14.7% ± 10.1%, mean ± SD) than asymptomatic chronic thrombocytosis patients (n = 23, RP% = 3.4% ± 1.8%), healthy controls (3.4% ± 1.3%), DVT patients (n = 21, 3.8% ± 2.1%), or ART patients (n = 25, 4.5% ± 4.1%, P < .05 for all comparisons). Chronic thrombocytosis patients with thrombosis also had significantly higher absolute RP counts than asymptomatic chronic thrombocytosis patients (98 ± 64 × 109/L [range, 54 to 249 × 109/L] v 30 ± 13 × 109/L [range, 11 to 51 × 109/L]; P = .0004), whereas healthy controls, DVT, and ART patients had similarly low absolute RP counts (6 ± 6 × 109/L, 9 ± 7 × 109/L, and 11 ± 7 × 109/L, respectively; P > .49). The RP% and absolute RP counts remained significantly higher in chronic thrombocytosis patients with thrombosis when patients were further subdivided into primary myeloproliferative disorders versus secondary thrombocytosis. Similarly elevated RP percentages and absolute counts were also noted in transient thrombocytosis patients with thrombosis (n = 6, 11.5% ± 4.4% and 90 ± 46 × 109/L, respectively) when compared with asymptomatic transient thrombocytosis patients (n = 40, 4.5% ± 2.7% and 35 ± 16 × 109/L, respectively) and to all control groups (P < .05 for all comparisons). In addition, 7 of 8 thrombocytosis patients who were studied before developing symptoms of thrombosis had elevated absolute RP counts compared with only 1 of 63 thrombocytosis patients who remained asymptomatic. Follow-up studies in seven chronic thrombocytosis patients showed that successful aspirin treatment of symptomatic recurrent thrombosis significantly reduced the RP% from 17.1% ± 10.9% before therapy to 4.8% ± 2.0% after therapy; absolute RP counts decreased from 102 ± 67 × 109/L to 26 ± 10 × 109/L (P < .01 for both). We conclude that thrombosis in the setting of an elevated platelet count is associated with increased platelet turnover, which is reversed by aspirin therapy. Measurement of reticulated platelets to assess platelet turnover may be useful in evaluating both treatment response and thrombotic risk in thrombocytosis.

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