Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019087 (hemorrhagic diathesis)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After a bite by the aglyphous red-necked keelback snake Rhabdophis subminiatus a complete defibrinogenation syndrome with severe hemorrhagic diathesis developed in a 25-year-old man. In vitro studies showed that the venom gland extract of the snake contains a very active prothrombin (Factor II) activator. The thrombin generated is inhibited neither by antithrombin III nor the antithrombin-III-heparin complex. The venom gland extract stimulated also the tissue plasminogen activator; however, it did not cause direct activation of plasminogen, protein C, Factor X or direct degradation of fibrinogen.
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PMID:Hemostatic changes due to the venom gland extract of the red-necked keelback snake (Rhabdophis subminiatus). 180 26

We recently described a new case of alpha 1-antithrombin (alpha 1-AT) Pittsburgh, a mutation that transforms alpha 1-AT into a potent inhibitor of thrombin. In contrast to the originally described patient, who had a severe hemorrhagic diathesis, our proband had only a mild bleeding tendency. The current article explores possible mechanisms for the relative hemostatic competence of our patient. The levels of both normal and mutant alpha 1-AT were similar to those of the previously reported case, as was the rise in plasma antithrombin level during an acute phase reaction. The level of protein C, however, was found on several occasions to be approximately 20% of normal. Family studies and examination of the patient's protein C gene on a denaturing gel failed to identify an abnormality. Moreover, the patient's protein C showed no abnormalities suggestive of faulty intracellular processing. However, the protein C in his plasma was for the most part in the activated form and bound to the mutant alpha 1-AT. Thus it is likely that the strong affinity of mutant alpha 1-AT for protein C leads to an increased turnover and thus to a low circulating level. A seeming flaw in that scenario is that the mutant alpha 1-AT also has a very high affinity for thrombin and might be expected therefore to block the activation of protein C. When thrombin was complexed with thrombomodulin (as it is when protein C is physiologically activated at the endothelial surface), mutant alpha 1-AT was far less able to inhibit thrombin than was the case for the free enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of protein C deficiency in a patient with arginine 358 alpha 1-antitrypsin (Pittsburgh mutation): role in the maintenance of hemostatic balance. 770 10

The lupus anticoagulant may be accompanied by an acquired factor II deficiency and bleeding. We report on a patient with a lupus anticoagulant and factor II (Fll) deficiency responsive to Danazol. Acquired hypoprothrombinemia (FII) with the lupus anticoagulant (LA) may be accompanied by a hemorrhagic diathesis. A 64-year-old male with discoid lupus erythematosis bled after an intestinal polypectomy. His FII level was 18%, and his FII antigen level was 20%. Danazol (D) (600 mg per day) administration was associated with a rise in FII activity and antigen to 50% within 10 days. The patient underwent abdominal surgery. We studied the effect(s) of D on the FII level and on other coagulation factors in this patient. The patient's plasma FII antigen had a single precipitin arc compared to the two peaks of normal plasma on counterimmunoelectrophoresis with Ca++. The samples pre- and during D therapy had the same positively charged arc as normal samples, although they were quantitatively different. Neuraminidase treatment demonstrated a decrease in the positively charged migration of normal and the patient's FII antigen. Affinity chromatography of normal and patient plasma on a Sepharose protein A column revealed FII antigen present in the patient's bound fraction. The relative percentages of bound FII before and during D treatment were similar. During D therapy, levels of FIX and X rose 50-100%, and protein C rose 20-25%, while free protein S did not change. D is an effective therapy for acquired FII deficiency associated with LA. D does not affect the binding of Ig to FII, but D raises FII levels by increasing synthesis of the FII protein.
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PMID:Acquired hypoprothrombinemia: effects of danazol treatment. 894 70

Clot formation is the final result of interaction among multiple plasma proteins; after activation, it results in the conversion of fibrinogen to fibrin and cross-linking of fibrin by activated factor XIII, which stabilizes the formed clot. Deficiency or functional abnormality of the factors involved in these reactions causes bleeding disorders. Natural inhibitors of clotting factors include antithrombin III, protein S, and protein C. When activated, these proteins inactivate specific clotting factors, providing a regulatory mechanism that serves to control the coagulation response and limit the extension of the clot. Physiologic or natural inhibitors should not be confused with acquired inhibitors of coagulation factors, which are discussed in this review. Inhibitors to coagulation factors, also known as circulating anticoagulants, are antibodies that neutralize specific clotting proteins, thereby interfering with their normal function. Antibodies may be directed against isolated clotting factors, as is the case with factor VIII or IX inhibitors. On the other hand, the antiphospholipid antibodies are known to develop against multiple coagulation proteins. In contrast to patients with antibodies against isolated clotting factors, who commonly present with spontaneous bleeding, individuals with antiphospholipid antibodies may be asymptomatic or present with venous or arterial thrombosis. In this article I refer to inhibitors developing in patients with hemophilia A or other congenital factor deficiency as alloantibodies, and to spontaneous formation of antibodies in patients without prior history of hemorrhagic diathesis as autoantibodies. The antiphospholipid antibodies are discussed separately.
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PMID:Inhibitors to clotting factors. 932 77

In a patient who presented with a severe coagulation deficiency in plasma contrasting with a very mild hemorrhagic diathesis a homozygous Arg67His mutation was identified in the prothrombin gene. Wild-type (factor IIa [FIIa]-WT) and mutant Arg67His thrombin (FIIa-MT67) had similar amidolytic activity. By contrast, the k(cat)/K(m) value of fibrinopeptide A hydrolysis by FIIa-WT and FIIa-MT67 was equal to 2.1 x 10(7) M(-1)s(-1) and 9 x 10(5) M(-1)s(-1). Decreased activation of protein C (PC) correlated with the 33-fold decreased binding affinity for thrombomodulin (TM; K(d) = 65.3 nM vs 2.1 nM, in FIIa-MT67 and in FIIa-WT, respectively). In contrast, hydrolysis of PC in the absence of TM was normal. The Arg67His mutation had a dramatic effect on the cleavage of protease-activated G protein-coupled receptor 1 (PAR-1) 38-60 peptide (k(cat/)K(m) = 4 x 10(7) M(-1)s(-1) to 1.2 x 10(6) M(-1)s(-1)). FIIa-MT67 showed a weaker platelet activating capacity, attributed to a defective PAR-1 interaction, whereas the interaction with glycoprotein Ib was normal. A drastic decrease (up to 500-fold) of the second-order rate constant pertaining to heparin cofactor II (HCII) interaction, especially in the presence of dermatan sulfate, was found for the FIIa-MT67 compared with FIIa-WT, suggesting a severe impairment of thrombin inhibition by HCII in vivo. Finally, the Arg67His mutation was associated with a 5-fold decrease of prothrombin activation by the factor Xa-factor Va complex, perhaps through impairment of the prothrombin-factor Va interaction. These experiments show that the Arg67His substitution affects drastically both the procoagulant and the anticoagulant functions of thrombin as well as its inhibition by HCII. The mild hemorrhagic phenotype might be explained by abnormalities that ultimately counterbalance each other.
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PMID:Molecular and functional characterization of a natural homozygous Arg67His mutation in the prothrombin gene of a patient with a severe procoagulant defect contrasting with a mild hemorrhagic phenotype. 1214 17

The acronym DIC is commonly interpreted as "death is coming". This pessimistic view emphasizes the deficiency of available treatment options following diagnosis of disseminated intravascular coagulation. Clinically, DIC manifests as a systemic hemorrhagic disorder associated with widespread activation and eventual exhaustion of the coagulation system, although events underlying DIC also involve effectors of inflammation. DIC can be associated with diverse conditions including sepsis and major trauma and, when identified, signifies a significant worsening in prognosis and expected mortality. Although recent clinical studies have shown that activated protein C reduces mortality in patients with severe sepsis, there is a need for further investigation and a better understanding of the underlying mechanisms.
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PMID:Alternative treatments for disseminated intravascular coagulation. 1533 73

The acronym DIC is commonly interpreted as "death is coming." This pessimistic view emphasizes the deficiency of available treatment options following diagnosis of disseminated intravascular coagulation. Clinically, DIC manifests as a systemic hemorrhagic disorder associated with widespread activation and eventual exhaustion of the coagulation system, although events underlying DIC also involve effectors of inflammation. DIC can be associated with diverse conditions including sepsis and major trauma and, when identified, signifies a significant worsening in prognosis and expected mortality. Although recent clinical studies have shown that activated protein C reduces mortality in patients with severe sepsis, there is a need for further investigation and a better understanding of the underlying mechanisms.
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PMID:Alternative treatments for disseminated intravascular coagulation. 1554 51

The methods of the prevention, diagnosis, and correction of hemostatic disorders are discussed in cardiosurgical patients. Prevention of hemorrhages requires hemostatic history data collection that allows identification of patients with concomitant hemophilia and those, taking antithrombotic drugs. The benefits of an extended study of blood coagulation disorders are shown in neonates and babies of the first year of life due to the physiological features of the hemostatic system and the pattern of heart disease. Algorithms are proposed for the diagnosis and treatment of hemorrhagic diathesis in the early postoperative period; a complex of minor signs of surgical hemorrhage is formulated, which makes it possible to timely perform rethoracotomy and to reduce blood transfusion. Efficiency evaluation and exclusion criteria for the use of recombinant factor VIIa are given. The efficiency of using the Russian drug tranexam versus epsilon-aminocapronic acid and aprotinin in the perioperative period was evaluated. The blood coagulative system was monitored in the treatment of disseminated intravascular coagulation in multiple organ dysfunction and sepsis, which promoted the timely use of recombinant human activated protein C and human antithrombin III. A diagnostic and treatment algorithm for replacement therapy of congenital heart disease concurrent with hemophilia A is given.
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PMID:[Diagnosis and correction of thrombohemorrhagic complications in cardiosurgical patients in the early postoperative period]. 2140 Jul 31