Effect of Purified Vipera Palestinae Hemorrhagin on Blood Coagulation and Platelet Function

1969 ◽  
Vol 22 (03) ◽  
pp. 482-495 ◽  
Author(s):  
L Grotto ◽  
Z Jerushalmy ◽  
A de Vries

SummaryPurified Vipera palestinae hemorrhagin (VPH) impairs thrombin formation, fibrinogen clottability, FSF activity, platelet clot retracting activity, ADP- and connective tissue-induced platelet aggregation and connective tissue - induced platelet ADP release. The effects of VPH became manifest or increased in intensity on incubation with the respective substrates prior to measurement of their activities. Inactivation of the VPH protease by DFP resulted in complete abolishment of the first four and partial inhibition of the last two of the above VPH activities.Administration of VPH to guinea pigs caused widespread hemorrhages, associated with moderate hypofibrinogenemia but normal platelet count, clotting time and clot retraction. DFP-treated VPH caused hemorrhage without hypofibrinogenemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1118-1118 ◽  
Author(s):  
Douglas B. Cines ◽  
Tatiana Lebedeva ◽  
M. Anna Kowalska ◽  
Mortimer Poncz ◽  
Lubica Rauova ◽  
...  

Abstract Abstract 1118 There are no currently available tests to rapidly assess and reliably identify both impaired hemostasis and hypercoagulable states, in part because of difficulties in measuring integrated reactions in whole blood using a single sensitive and clinically useful platform. Methods like T2 magnetic resonance (T2MR) can provide rich information from complex samples, such as changes in the blood during hemostasis, by measuring signals emanating from the hydrogen nuclei within the sample, primarily in water. We used a 14”x6”x7” portable instrument to measure changes in T2MR that provide a continuous report on the dynamically changing microscopic environment of water during coagulation of whole blood (WB), platelet-poor or platelet-rich plasma (PRP). In these initial foundational studies, we measured T2MR continuously over 20 mins using 34 μL blood samples from consented normal adult donors. We tested clotting of WB initiated by the addition of thrombin or kaolin + calcium. Platelet activation was achieved in WB by addition of ADP or arachidonic acid in the presence of reptilase and factor XIIIa with and without addition of the platelet inhibitors aspirin or 2-methylthioadenosine 5'-monophosphate (2-MeSAMP) and results were confirmed by standard platelet aggregometry. At normal platelet counts from 1.5–3×105/μL and normal hematocrit (HCT) from 38%-48%, T2MR gave two curves corresponding to: (1) water trapped within a retracted clot and (2) water in the surrounding liquid, i.e. serum (Fig. 1a). Platelet counts <1×105/μL or addition of aspirin or 2-MeSAMP eliminated the signal originating from clot retraction (Fig. 1b). High platelet counts (3–13×105/μL) and high thrombin concentrations (10 u/mL) led to a third, even more highly ordered signal (Fig. 1c). The signal also revealed the influence of hematocrit on clot formation/retraction over a wide range of values (20%-73%). Platelet inhibition by aspirin or 2-MeSAMP decreased or eliminated the signal originating from clot retraction (Fig. 1d). Our proof-of-principle studies show that T2MR technology can be applied to measurement of blood clotting across a range of hemostatic conditions. This single technology may be applicable to the study, diagnosis, and management of a spectrum of disorders that range from impaired hemostasis to hypercoagulable states. These T2MR studies represent the first application of this technology to hemostasis and thrombosis. Additional studies will be needed to develop a more complete understanding of the biochemical events measured by T2MR and to more fully explore its clinical utility. Figure 1. Examples of T2MR 3D surfaces for 34 μL of citrated whole blood mixed activated by adding a dried formulation of CaCl2 (11 mM) and kaolin (<0.25%) for (a) a normal platelet count (2.82×105 platelets/μL); (b) thrombocytopenia (9.0×104 platelets/μL); and (c) thrombocytosis (1.0×106 platelets/μL). All samples were reconstituted blood in the same way. (d) Citrated whole blood activated by ADP in the presence of 2-MeSAMP. Figure 1. Examples of T2MR 3D surfaces for 34 μL of citrated whole blood mixed activated by adding a dried formulation of CaCl2 (11 mM) and kaolin (<0.25%) for (a) a normal platelet count (2.82×105 platelets/μL); (b) thrombocytopenia (9.0×104 platelets/μL); and (c) thrombocytosis (1.0×106 platelets/μL). All samples were reconstituted blood in the same way. (d) Citrated whole blood activated by ADP in the presence of 2-MeSAMP. Disclosures: Cines: T2 Biosystems: Research Funding. Lebedeva:T2 Biosystems: Research Funding. Massefski:T2 Biosystems: Employment. Papkov:T2 Biosystems: Employment. Thayer:T2 Biosystems: Employment. Lowery:T2 Biosystems: Employment.


1975 ◽  
Vol 33 (02) ◽  
pp. 278-285 ◽  
Author(s):  
Şeref Inceman ◽  
Yücel Tangün

SummaryA constitutional platelet function disorder in a twelve-year-old girl characterized by a lifelong bleeding tendency, prolonged bleeding time, normal platelet count, normal clot retraction, normal platelet factor 3 activity and impaired platelet aggregation was reported.Platelet aggregation, studied turbidimetrically, was absent in the presence of usual doses of ADP (1–4 μM), although a small wave of primary aggregation was obtained by very large ADP concentrations (25–50 μM). The platelets were also unresponsive to epinephrine, thrombin and diluted collagen suspensions. But an almost normal aggregation response occurred with strong collagen suspensions. The platelets responded to Ristocetin. Pelease of platelet ADP was found to be normal by collagen and thrombin, but impaired by kaolin. Platelet fibrinogen content was normal.The present case, investigated with recent methods, confirms the existence of a type of primary functional platelet disorder characterized solely by an aggregation defect, described in 1955 and 1962 under the name of “essential athrombia.”


2018 ◽  
Vol 35 (6) ◽  
pp. 671-675 ◽  
Author(s):  
Emily Ankus ◽  
Sarah J Price ◽  
Obioha C Ukoumunne ◽  
William Hamilton ◽  
Sarah E R Bailey

1959 ◽  
Vol 196 (5) ◽  
pp. 1015-1019 ◽  
Author(s):  
Harrison H. Shoulders ◽  
Robert C. Hartmann ◽  
H. C. Meng

A fat emulsion prepared for intravenous administration has been studied with regard to its effect upon blood coagulation in dogs. The most characteristic effects found during intravenous infusion of this material at a rate of 1 ml/min. were thrombocytopenia and marked shortening of clotting time. These effects were invariably observed in animals which had not previously received the emulsion. When subsequent infusions were given within 3 hours, no significant changes were observed. When the interval was extended to 1–13 days, variable responses occurred, at times characterized by pronounced hypocoagulability. If the repeat infusion was given 2 weeks or more after the initial one, the effects were similar to those observed during the first infusion. The prothrombin and thrombin clotting times and plasma fibrinogen concentration were not greatly altered during the infusion. Abnormal bleeding time, ‘prothrombin utilization’ and clot retraction accompanied the thrombocytopenia.


Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 74-81 ◽  
Author(s):  
DJ Kuter ◽  
RD Rosenberg

Abstract The relationship between the bone marrow (BM) megakaryocyte and the circulating platelet was explored. Incremental changes in platelet count were made in rats by infusion of antiplatelet antibody or by platelet transfusion, and the response of megakaryocytes was measured by flow cytometry. Proportional changes in megakaryocyte ploidy were demonstrated: As the platelet count declined, ploidy increased; as the platelet count increased, ploidy decreased. Even moderate degrees of thrombocytopenia and thrombocytosis (48% and 177% of the normal platelet count) were associated with changes in ploidy. These changes were not the results of the technique used to alter the platelet count because reinfusion of platelets after 3 hours of thrombocytopenia prevented any ploidy change. These studies proved that the circulating platelet and the megakaryocyte constitute a classic feedback loop whose activity can be measured by the degree of ploidization of the megakaryocyte. The minimal duration of thrombocytopenia necessary to promote megakaryocyte ploidy changes was approximately 10 hours. Using a BM culture assay, we identified a plasma factor which induced alterations in megakaryocyte ploidy and whose level is inversely proportional to the platelet count.


1979 ◽  
Vol 16 (2) ◽  
pp. 229-242 ◽  
Author(s):  
C. M. Forsberg ◽  
V. E. O. Valli ◽  
P. W. Gentry ◽  
R. M. Donworth

Blood coagulation studies showed there was a pronounced thrombocytopenia and hypofibrinogenemia in Holstein calves infected with Trypanosoma congolense TREU 112. There was also ineffective thrombopoiesis characterized by an increased megakaryocytic mass, reduced uptake of 35S-methionine into peripheral blood platelets and a normal platelet lifespan. There was an increased uptake of isotopic label into fibrinogen and a shortened half life indicating a consumptive error with increased peripheral use of fibrinogen. No consistent abnormalities were found in ethanol gelation, partial thromboplastin time, clot retraction and lysis or plasminogen assay. Fibrin split products were rarely detected. These findings suggest that in the chronic form of bovine trypanosomiasis there is a partially compensated consumption coagulopathy.


Blood ◽  
1961 ◽  
Vol 18 (1) ◽  
pp. 73-88 ◽  
Author(s):  
SIDNEY L. SALTZSTEIN

Abstract Accumulation of a lipid, histochemically a phospholipid, in the histiocytes of the splenic pulp was observed in seven patients with thrombocytopenic purpura. Six had classical idiopathic thrombocytopenic purpura with abundant megakaryocytes in the bone marrow. Splenectomy resulted in clinical and hematologic remissions in four of these six, continued thrombocytopenia in the fifth, and in the continued requirement of corticosteroid to maintain a reasonably normal platelet count in the sixth. The seventh patient, who died shortly after splenectomy, had marked hypoplasia of megakaryocytes. Similar lipid accumulation was not seen in more than 700 other spleens, removed for a variety of reasons, reviewed in this study. Platelet phagocytosis has been suggested as a source of the lipid.


1997 ◽  
Vol 33 (5) ◽  
pp. 411-415 ◽  
Author(s):  
LE Smedile ◽  
DM Houston ◽  
SM Taylor ◽  
K Post ◽  
GP Searcy

The medical records of 11 Cavalier King Charles spaniels with idiopathic, asymptomatic thrombocytopenia and large-to-giant platelets were identified from a 10-year retrospective search using the Veterinary Medical Data Base at Purdue University. Eight of the dogs had been treated with various immunosuppressive drugs. Six of the treated dogs remained thrombocytopenic, one was not reevaluated, and one developed a normal platelet count. The underlying etiology of idiopathic, asymptomatic thrombocytopenia in Cavalier King Charles spaniels has not been identified, but this condition could represent a congenital macrothrombocytopenic disorder.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2895-2895
Author(s):  
Gail A. Rock ◽  
David Anderson ◽  
Barrett Benny ◽  
David Barth ◽  
William Clark ◽  
...  

Abstract Introduction The ultimate therapy for TTP is not yet defined. While approximately 85% of patients respond to plasma exchange with FFP, the use of alternative solutions such as cryosupernatant plasma, which is deficient in the high molecular weight forms of vWF. has not been proven by appropriate randomized prospective sample trials. However, it is intellectually appealing. Additionally, the use of the ADAMTS 13 level either to predict disease or outcome has not been resolved. Methods Cryosupernatant plasma (CSP) was compared to solvent detergent treated plasma (SDP) over one cycle (nine days) of plasma exchange (PE) and subsequent procedures as required. Throughout treatment, ADAMTS 13 and protein S levels were followed. Results At the primary end point of one month, 3 of 35 of the CSP and 1 of 27 of the SDP patients died. The average platelet count was 184 × 109 per litre for CSP and 209 × 109 per litre for SDP. While vWF and FVIII were elevated in all patients at entry, no unusually large vWF multimers were seen at any time. At entry 9 patients had ≤ 0–10% ADAMTS 13 and 14 of 62 had normal levels with the rest in between. At presentation only 9 patients had 100% inhibitor activity with no inhibitor in 18 patients. Of the four patients who died, two who received CSP, had 100% enzyme activity at presentation whereas one had no ADAMTS-13 and another had 10%. All 4 patients died within 10 days. Fifteen patients with less than 10% enzyme activity had >1.5 vWF. However, elevated (>3u/mL) vWF was seen in the presence of normal ADAMTS-13 levels. Six months after remission, and in the presence of a normal platelet count, ADAMTS13 remained low in 5 patients and normal in 15.Protein S levels in 41/62 patients studied showed little variation during therapy with values on day 3 and 5, similar to those seen on entry. Conclusion In idiopathic TTP, ADAMTS 13 levels do not correlate with disease, and are not predictive of outcome. While protein S levels in the SDP were lower than those found in FFP, this did not appear to have clinical significance.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18531-e18531
Author(s):  
Jiwen Wang ◽  
Min Luo ◽  
Hanmo Wu ◽  
Liming Sheng ◽  
Dan Su ◽  
...  

e18531 Background: Activated platelet is thought to promote cancer cells growth and metastasis, playing an important role in progression of cancer. However, the association between platelet counts and prognosis of patient with non small cell lung cancer (NSCLC) had not been fully elucidated. The aim of this study is to investigate the prognostic value of platelet counts in resectable NSCLC. Methods: A total of 636 primary NSCLC patients who had curatively resected surgery in Zhejiang Cancer Hospital from November 2006 to January 2011 were retrospectively analyzed. Preoperative platelet counts and clinicopathological factors were collected from the medical record database. Patients were followed up for disease progression free survival (PDS) and overall survival (OS) until January 20, 2013. The association between platelet counts and patients’ outcome were evaluated. Results: In all patients, 13.8% (88/636) had increased platelet count (>300 × 109/L), referred to as thrombocytosis. The proportion of thrombocytosis was significantly higher in male, squamous-cell carcinoma and stage III than that in female, other histological types and early stage NSCLC. Moreover, thrombocytosis was associated with significantly shortened survival. Multivariate Cox analysis showed patient with thrombocytosis not only had a 1.66 time elevated risk for disease progression (95% CI, 1.14-2.41, p=0.009), but also had and a 1.47 time risk for death (95% CI, 1.04-2.08, P=0.029), compared with that in those having normal platelet count. More interestingly, the risk for replase was increased to 3.19 times (95% CI, 1.41-7.23, p=0.006) in stage I NSCLC with thrombocytosis than that in patients with normal platelet count after stratified analysis by stage. Conclusions: Preoperative platelet count is an independent prognostic predictor in operable NSCLC, especially in early stage I NSCLC. Platelet count may serve as a useful indicator and potential target for personalized treatment with antiplatelet reagent.


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