Suppressive Effect of Dextran on Platelet Adhesiveness

Summary43 normal volunteers, 3 patients with thrombophlebitis, and 1 patient with a high platelet adhesiveness and a history of thrombophlebitis have received dextran and its action on the mechanism of haemostasis has been studied. Platelet adhesiveness has been investigated by a slight modification of Hellem’s methods for whole blood and plasma. Dextran with a mean molecular weight of 70,000 produced a markedly lowered platelet adhesiveness together with a moderate prolongation of the Ivy bleeding time. Factor VIII was decreased by about 50% and factor V, factor IX and fibrinogen were decreased slightly more than could be expected from haemodilution alone. No fibrinolysis occurred. Dextran of lower molecular size was less potent. The possible use of dextrans as a thrombosis prophylactic agent is discussed.

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The Effect of Dextran of Various Molecular Weight on the Coagulation in Dogs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654535 ◽

1961 ◽

Vol 06 (01) ◽

pp. 015-024 ◽

Cited By ~ 32

Author(s):

Sven Erik Bergentz ◽

Oddvar Eiken ◽

Inga Marie Nilsson

Keyword(s):

Molecular Weight ◽

Body Weight ◽

High Molecular Weight ◽

Bleeding Time ◽

Factor Vii ◽

Low Molecular Weight ◽

Factor V ◽

Coagulation Mechanism ◽

Coagulation Defects

Summary1. Infusions of low molecular weight dextran (Mw = 42 000) to dogs in doses of 1—1.5 g per kg body weight did not produce any significant changes in the coagulation mechanism.2. Infusions of high molecular weight dextran (Mw = 1 000 000) to dogs in doses of 1—1.5 g per kg body weight produced severe defects in the coagulation mechanism, namely prolongation of bleeding time and coagulation time, thrombocytopenia, pathological prothrombin consumption, decrease of fibrinogen, prothrombin and factor VII, factor V and AHG.3. Heparin treatment of the dogs was found to prevent the decrease of fibrinogen, prothrombin and factor VII, and factor V otherwise occurring after injection of high molecular weight dextran. Thrombocytopenia was not prevented.4. In in vitro experiments an interaction between fibrinogen and dextran of high and low molecular weight was found to take place in systems comprising pure fibrinogen. No such interaction occurred in the presence of plasma.5. It is concluded that the coagulation defects induced by infusions of high molecular weight dextran are due to intravascular coagulation.

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A Case of FVII Inhibitor.

Blood ◽

10.1182/blood.v116.21.3655.3655 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3655-3655

Author(s):

Michael Joshua Levitt ◽

Arthur A. Topilow ◽

William Lerner ◽

Peter Mencel ◽

Carl Henningson ◽

...

Keyword(s):

Research Funding ◽

Immunosuppressive Treatment ◽

Factor Ix ◽

Factor Vii ◽

Factor V ◽

First Line ◽

Immunosuppressive Medications ◽

Factor Ii ◽

Plasma Factor ◽

History Of

Abstract Abstract 3655 Acquired inhibitors of coagulation are bleeding disorders that require prompt recognition, diagnosis, and management. Antibodies against factor VII are extremely rare with only a few cases reported in the literature. We present a case of a patient with an acquired Factor VII inhibitor. This is an 87 year old female with a past medical history of breast cancer, hypertension, and hyperlipidemia who presented to the emergency room with right flank pain and hematuria. A CT scan of the abdomen and pelvis showed bilateral hydronephrosis with no evidence of nephrolithiasis. The patient denied hematemesis or hematochezia but was noted to have hemoccult positive stools. The patient denied any anticoagulant use. Admission laboratories revealed a coagulopathy with a normal partial thromboplastin time (PTT) of 28 seconds and prolonged prothrombin time (PT) of greater than 50 seconds and INR of 19.59. The patient received vitamin K without improvement in coagulation parameters. A mixing study revealed a markedly prolonged PT that did not correct with 1:1 (18.9 seconds) and 4:1 (27.3 seconds) mix normal plasma. Factor assays shows an abnormal Factor VII level of less than 1%, and normal Factor II 121%, Factor V 140%, Factor VIII 201%, Factor IX 99%, and Factor XI 126% levels. A FVII inhibitor was 1.66 Bethesda units per milliliter. Immunosuppressive treatment was initiated with prednisone 1 milligram per kilogram daily and cyclophosphamide 200 milligrams daily. Factor VII levels normalized without evidence of inhibitor. The patient clinically improved and immunosuppressive medications were gradually tapered off. This case emphasizes the importance of prompt recognition in a patient with a rare acquired inhibitor of coagulation. Treatment with immunosuppressive therapy consisting of corticosteroids and cyclophosphamide resulted in normalization of factor VII levels and resolution of bleeding symptoms and should be considered as first-line management for such patients. Disclosures: Philipp: Baxter: Research Funding; Wyeth: Research Funding; Octapharma: Research Funding.

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Hemophilia

Pediatrics in Review ◽

10.1542/pir.12.9.275 ◽

1991 ◽

Vol 12 (9) ◽

pp. 275-281

Author(s):

Jeanne M. Lusher ◽

Indira Warrier

Keyword(s):

Bleeding Time ◽

Soft Tissues ◽

Hemophilia A ◽

Factor Ix ◽

Hemophilia B ◽

Screening Tests ◽

Cord Blood Sample ◽

Family Pedigree ◽

History Of ◽

Von Willebrand

Hemophilia is a hereditary bleeding disorder characterized by Factor VIII (F-VIII) or Factor IX (F-IX) deficiency, bleeding into joints and soft tissues, and an X-linked mode of inheritance. Approximately one third of new cases occur as spontaneous mutations, with no family history of hemophilia. The incidence of hemophilia is about one per 20 000 persons, and one per 10 000 males. DIAGNOSIS Hemophilia A (characterized by F-VIII deficiency) and hemophilia B (characterized by F-IX deficiency) are clinically indistinguishable. Both affect males almost exclusively; both have the same type of bleeding; and, if the usual coagulation screening tests are performed, both are characterized by a prolonged partial thromboplastin time and normal prothrombin time. The template bleeding time is usually normal; this is expected, because the bleeding time is a reflection of platelet numbers, platelet function, capillary integrity, and von Willebrand factor activity, all of which are normal in the case of hemophilia. Hemophilia A and hemophilia B can be separated by assaying F-VIII and F-IX. Because neither F-VIII nor F-IX crosses the placenta, the diagnosis can be made at birth by obtaining a cord blood sample for assay. CARRIER DETECTION AND PRENATAL DIAGNOSIS Carriers of the hemophilia gene may be "obligate" carriers, in the sense that the family pedigree indicates that a particular female must be carrying the gene for F-VIII (or F-IX) deficiency.

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Haemostasis and High Altitude

10.1055/s-0039-1682425 ◽

1977 ◽

Author(s):

I. Singh ◽

I.S. Chohan

Keyword(s):

Factor Viii ◽

High Altitude ◽

Bleeding Time ◽

Clot Lysis ◽

Factor Xii ◽

Factor V ◽

Platelet Adhesiveness ◽

Clot Retraction ◽

Platelet Factor ◽

Lysis Time

On arrival at high altitude there is a tendency towards hypercoaguiation associated with an increase in platelet count, factors X and XII, and thrombo-test activity (TA) which is reflected by decrease in prothrombin time (PT), bleeding time (BT), clotting time in glass (CT-gl) and in silicone (CT-sl), and stypven time (ST). Clot retraction is impaired. This hypercoaguiation state is countered by a compensatory rise in fibrinolytic activity reflected by reduction of clot lysis time (CLT), plasma fibrinogen, and factor VIII.This hypercoaguiation state persists throughout the early fortnight after arrival at high altitude and then starts regressing. On day 3, factor V decreases, BT, and ST are further reduced, and factor VIII shows a rise. On day 7, a progressive rise occurs in factors V, VIII, X and XII, TA, platelet counts and platelet factor 3 (PF-3).CT-gl, CT-sl, PT and ST are further shortened. On day 14, haematocrit rises and of all the parameters, factors V and X and clot retraction return to normal. Throughout the fortnight, factor XII remains high, CLT is short, and platelet adhesiveness remains within normal range.After 2 years’ stay at high altitude, a regression in hypercoagulability occurs and is indicated by persistent short CLT, prolonged BT, CT-sl, PT, ST and reduced TA. Platelet adhesiveness, PF-3, factors V, VIII and XII and clot retraction are restored to normal.

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Further Studies on the Effect of Dextran of Various Molecular Weight on the Coagulation Mechanism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654804 ◽

1964 ◽

Vol 11 (01) ◽

pp. 038-050 ◽

Cited By ~ 21

Author(s):

Inga Marie Nilsson ◽

Oddvar Eiken

Keyword(s):

Molecular Weight ◽

Body Weight ◽

Platelet Count ◽

Bleeding Time ◽

Average Molecular Weight ◽

Coagulation Factors ◽

Factor Vii ◽

Factor V ◽

Human Beings ◽

Coagulation Defect

SummaryDextran fractions of different molecular weights were given to dogs in order to ascertain at which molecular weight dextran interferes with the coagulation factors.1. Infusions of dextran with an average molecular weight of 130,000 (Intradex®) and in doses of 1.5 g dextran per kg body weight induced a moderate coagulation defect. There was a slight prolongation of the bleeding time and a slight drop in platelet count. Values for AHF, factor V, prothrombin and factor VII, and fibrinogen declined by 10 to 40% of the original values.2. Infusions of dextran with an average molecular weight of 75,000 (Macrodex®) in doses of 1.5 g per kg body weight did not produce any significant changes in bleeding time and platelet count. The AHF level decreased by 40% and the levels of prothrombin and factor VII, factor V and fibrinogen by about 10% of the original values. In a dose of 2 g per kg body weight this fraction produced a significant coagulation defect with a fall of the various coagulation factors by about 40 to 50%.3. A dextran fraction with an average molecular weight of 60,000 in doses of 1.5 g per kg body weight did not prolong the bleeding time and caused only a very slight decrease in platelet count. There were no changes in the values for AHF, factor V, prothrombin and factor VII but a slight drop occurred in the fibrinogen levels.4. Dextran with an average molecualr weight of 40,000 (Rheomacrodex ® ) in doses of 1.5 g per kg body weight did not affect the bleeding time or the platelet count. Nor did any significant decline occur in the amounts of the other coagulation factors.No changes in the Duke or in the Ivy bleeding times were observed in human beings given Macrodex® and Rheomacrodex® in doses of 1 g per kg body weight.Intradex® and Macrodex® in doses of up to 1-1.5 g per kg bodyweight to persons with normal blood coagulation are considered not associated with any appreciable risk of haemorrhage, but they are contraindicated in patients with haemorrhagic diathesis. The experiments indicate that Rheomacrodex® in similar doses does not incur any risk of haemorrhage.

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Subcellular Localization and Secretion of Factor V by Human Platelets

10.1055/s-0039-1682667 ◽

1977 ◽

Author(s):

D.D. Pifer ◽

R.W. Colman ◽

C.Mcl. Chesney

Keyword(s):

Molecular Weight ◽

Subcellular Localization ◽

Gel Filtration ◽

Molecular Size ◽

Apparent Molecular Weight ◽

Human Platelets ◽

Factor V ◽

Platelet Factor ◽

Dense Granules ◽

Plasma Factor

Previous studies have suggested that factor V in platelets is derived from plasma. In order to test this hypothesis, we studied the subcellular localization, release by aggregating agents, molecular size, and stability of factor V in human platelets. When platelet homoge-nates were fractionated on sucrose density gradient the factor V activity distributed primarily into the granules (0.076 units factor V activity/mg protein) with less amounts in the membrane fraction (0.014 units/mg protein) and virtually none in the dense granules or cytosol. Collagen released 79-3% of total platelet factor V clotting activity while ADP and epinephrine failed to liberate factor V activity, further supporting significant localization in the lysozomal granules rather than the dense granules. Platelet factor V can be solubilized by 0.1% Triton and has an apparent molecular weight of 470,000 as determined by 4% agarose gel filtration. In contrast, plasma factor V in the presence or absence of Triton has a molecular weight of 300,000. Factor V activity from the platelet homogenate exhibited biphasic decay at 37°C, suggesting more than one form, whereas plasma factor V shows a first order decay curve. These data suggest that platelet factor V is predominantly localized in the granules and is an intrinsic constituent of the platelet with different properties from plasma V.

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Von Willebrand Disease Combined with Factor V Deficiency: Variant Bari

10.1055/s-0039-1682594 ◽

1977 ◽

Author(s):

N. Ciavarella ◽

F.A. Scaraggi ◽

M. Petronelli ◽

M. Coviello ◽

A. Oreste ◽

...

Keyword(s):

Bleeding Time ◽

Von Willebrand Disease ◽

The Other ◽

Hemorrhagic Diathesis ◽

Factor V ◽

Factor V Deficiency ◽

New Variant ◽

History Of ◽

Von Willebrand ◽

Combined Deficiency

We report a new variant of the von Willebrand’disease combined with a deficiency of Factor V. A 35 yr. old woman presented a history of severe hemorrhagic diathesis with prolonged epistaxis, gum bleeding and menometrorrhagias, one of which caused hysterectomy. PT 24"/15", aPTT 70"/33", F.V 8%; Template Ivy Bleeding Time (BT) 15'-10'; VIIIC 7%, VIIIRAG 76%, VIIIWF 48%; Platelet Retention (PR) 95%; Ristocetin-Induced Platelet Aggregation (RIPA) > 2.0 mg/ml; Electrophoretic mobility was normal. Other plasmatio and platelet assays were normal. The propositus has two female children. One presented: BT 5'30" - 6'30"; F.V 137%; VIIIC 54%, VIIIRAG 66%, VIIIWF 56%. The other. BT 5'-8"; F.V 107%; VIIIC 29%, VIIIRAG 30%, VIIIWF 37%. One of her two sisters has F.V 53%. The other was normal. One of her two brothers has VIIIC 84%, VIIIRAG 65%, VIIIWF 52%. The other was normal. As her father died of a severe hemorrhagic episode, we studied her three aunts. One has VIIIC 44%. Another has BT 7'30" and F.V “borderline. The third has F.V “borderline. In all the subjects presented PR was normal, while in all but two RIPA was reduced. This new variant may represent a genetical link between the von Willebrand’disease and a combined deficiency of F.VIII and F.V.

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ITI with high-dose FIX and combined immunosuppressive therapy in a patient with severe haemophilia B and inhibitor

Hämostaseologie ◽

10.1055/s-0037-1617018 ◽

2009 ◽

Vol 29 (02) ◽

pp. 155-157 ◽

Cited By ~ 22

Author(s):

H. Hauch ◽

J. Rischewski ◽

U. Kordes ◽

J. Schneppenheim ◽

R. Schneppenheim ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Immunosuppressive Agents ◽

Tolerance Induction ◽

Intravenous Immunoglobulins ◽

Factor Ix ◽

High Dose ◽

Allergic Reactions ◽

Success Rates ◽

Serious Infections ◽

History Of

SummaryInhibitor development is a rare but serious event in hemophilia B patients. Management is hampered by the frequent occurrence of allergic reactions to factor IX, low success rates of current inhibitor elimination protocols and the risk of development of nephrotic syndrome. Single cases of immune tolerance induction (ITI) including immunosuppressive agents like mycophenolat mofetil (MMF) or rituximab have been reported. We present a case of successful inhibitor elimination with a combined immune-modulating therapy and high-dose factor IX (FIX). This boy had developed a FIX inhibitor at the age of 5 years and had a history of allergic reactions to FIX and to FEIBA→. Under on-demand treatment with recombinant activated FVII the inhibitor became undetectable but the boy suffered from multiple joint and muscle bleeds. At the age of 11.5 years ITI was attempted with a combination of rituximab, MMF, dexamethasone, intravenous immunoglobulins and high-dose FIX. The inhibitor did not reappear and FIX half-life normalized. No allergic reaction, no signs of nephrotic syndrome and no serious infections were observed.

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Dermatan Sulfate and LMW Heparin Enhance the Anticoagulant Action of Activated Protein C

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614856 ◽

1999 ◽

Vol 82 (11) ◽

pp. 1462-1468 ◽

Cited By ~ 22

Author(s):

José Fernández ◽

Jari Petäjä ◽

John Griffin

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Protein C ◽

Dermatan Sulfate ◽

Anticoagulant Activity ◽

Activated Protein C ◽

Factor V ◽

Factor Va ◽

Anticoagulant Action

SummaryUnfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

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The Activation of Human Factor IX

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647849 ◽

1975 ◽

Vol 33 (03) ◽

pp. 553-563 ◽

Cited By ~ 7

Author(s):

B Østerud ◽

K Laake ◽

H Prydz

Keyword(s):

Molecular Weight ◽

Sodium Dodecyl ◽

Apparent Molecular Weight ◽

Factor Ix ◽

Factor Vii ◽

Activate Factor ◽

Human Factor Ix ◽

Factor Xia ◽

Tissue Thromboplastin ◽

Native Factor

SummaryThe activation of factor IX purified from human plasma has been studied. Factor XIa and kallikrein separately activated factor IX to factor IXa. In both cases factor IX a had an apparent molecular weight of about 42–45000 in sodium dodecyl sul-phate-polyacrylamide disc gel electrophoresis compared with a molecular weight of about 70000 for the native factor IX. The activation by XIa required Ca2+-ions whereas Ca2+-ions did not influence the activation by kallikrein. A mixture of tissue thromboplastin and factor VII or RusselPs-viper venom alone did not activate factor IX. Trypsin activated and plasmin inactivated factor IX.

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