PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Coagulation Protein Disorders”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2000

Coagulation tests and anti-phospholipid antibodies in patients positive for lupus anticoagulant.

We examined activated partial thromboplastin time, kaolin clotting time, mixing with normal plasma in kaolin clotting time, dilute Russell's viper venom time, dilute Russell's viper venom time at high lipid concentrations, anti-phospholipid antibodies, and anti-cardiolipin-beta2-glycoprotein I complex antibody in 135 patients with prolongation of activated partial thromboplastin time and diagnosed 86 patients positive for lupus anticoagulant. The sensitivity of activated partial thromboplastin time and dilute Russell's viper venom time/dilute Russell's viper venom time-high lipid concentrations ratio for lupus anticoagulant were markedly high, but the specificity of activated partial thromboplastin time for lupus anticoagulant was not markedly high. The specificity, but not the sensitivity, of kaolin clotting time-mixing with normal plasma in kaolin clotting time was markedly high. In summary, dilute Russell's viper venom time to dilute Russell's viper venom time-high lipid concentrations ratio gave high sensitivity as well as specificity, being the only assay to confirm this. Of the patients positive for lupus anticoagulant, 25% were positive for anti-phospholipid antibodies and 17% were positive for anti-cardiolipin-beta2-glycoprotein I complex antibody. Of the lupus anticoagulant-positive patients with thrombosis, 45% were positive for anti-phospholipid antibodies, 35% were positive for anti-cardiolipin-beta2-glycoprotein I complex antibody, 60% were positive for both anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody, and only 17% were negative for anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody. These findings suggest that lupus anticoagulant can be diagnosed by dilute Russell's viper venom time/dilute Russell's viper venom time-high lipid concentrations ratio, and that thrombosis in lupus anticoagulant-positive may be predictable from both anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody. Plasma tissue type plasminogen activator level in lupus anticoagulant patients was significantly increased, and plasma tissue type plasminogen activator and fibrin-D-dimer levels in lupus anticoagulant-positive patients with thrombosis were significantly higher than in those without thrombosis, suggesting that the diagnosis of thrombosis by hemostatic markers might be important in lupus anticoagulant.

Adult↗
PubMed2004

Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors.

Hereditary combined deficiency of the vitamin K-dependent coagulation factors II, VII, IX, X, protein C, S and protein Z (VKCFD) is a very rare autosomal recessive inherited bleeding disorder. The phenotype may result from functional deficiency of either the gamma-glutamyl carboxylase (GGCX) or the vitamin K epoxide reductase (VKOR) complex. We report on the third case of VKCFD1 with mutations in the gamma-glutamyl carboxylase gene, which is remarkable because of compound heterozygosity. Two mutations were identified: a splice site mutation of exon 3 and a point mutation in exon 11, resulting in the replacement of arginine 485 by proline. Screening of 100 unrelated normal chromosomes by restriction fragment length polymorphism and denaturing high-performance liquid chromatography analysis excluded either mutation as a frequent polymorphism. Substitution of vitamin K could only partially normalize the levels of coagulation factors. It is suggested that the missense mutation affects either the propeptide binding site or the vitamin K binding site of GGCX.

Amino Acid Sequence↗
PubMed2001

Improved confirmation of weak lupus anticoagulants by employing sensitive and insensitive reagents to the lupus anticoagulant.

Detection of a lupus anticoagulant (LA) is of major importance to detect a thrombotic tendency. Confirmation of its phospholipid dependency may represent a tricky step in the diagnostic algorithm for LA, as several tests may yield borderline results of little diagnostic help. To improve on this point, we had previously employed a procedure comparing sensitive [rabbit brain kaolin (RBK)] and insensitive [soy bean phosphatides (SBP)] reagents to LA to screen and confirm LA at the same time in activated partial thromboplastin systems (aPTT). Here we compared its performance against a platelet neutralization procedure (PNP). To allow comparisons of our procedures with the PNP, a percentage ratio correction was calculated according to the following formula: [(RBK ratio - SBP ratio) x 100]/ RBK ratio. Similarly for the PNP: percentage ratio correction = [(buffer ratio - platelet phospholipid ratio) x 100]/buffer ratio. On 44 known LA plasmas, the PNP, expressed in seconds, yielded 15 (34%) negative or borderline results. After ratio transformation, the PNP still yielded 10 of 15 (66%) uncertain results, whereas the RBK/SBP procedure did not give any uncertain results (P = 0.0002). The mean percentage ratio correction was far superior for the RBK/SBP procedure than for the PNP (53.24 +/- 15.93 versus 20.28 +/- 12.15%, P < 0.0001). The use of sensitive and insensitive reagents to the lupus anticoagulant increases the confirmatory yield of LA in aPTT systems and may deserve inclusion amongst the confirmatory procedures for its diagnosis.

Anticoagulants↗
PubMed2003

Spontaneous intracerebral hemorrhage due to coagulation disorders.

Although intracranial hemorrhage accounts for approximately 10 to 15% of all cases of stroke, it is associated with a high mortality rate. Bleeding disorders account for a small but significant risk factor associated with intracranial hemorrhage. In conditions such as hemophilia and acute leukemia associated with thrombocytopenia, massive intracranial hemorrhage is often the cause of death. The authors present a comprehensive review of both the physiology of hemostasis and the pathophysiology underlying spontaneous ICH due to coagulation disorders. These disorders are divided into acquired conditions, including iatrogenic and neoplastic coagulopathies, and congenital problems, including hemophilia and rarer diseases. The authors also discuss clinical features, diagnosis, and management of intracranial hemorrhage resulting from these bleeding disorders.

Adolescent↗
PubMed2000

Effect of citrate concentration on coagulation test results in dogs.

OBJECTIVE: To determine the effect of citrate concentration (3.2 vs 3.8%) on coagulation tests in dogs. DESIGN: Original study. ANIMALS: 30 clinically healthy dogs and 12 dogs with hereditary hemostatic disorders. PROCEDURE: Blood was collected from all dogs directly into collection tubes containing 3.2 or 3.8% buffered citrate. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen concentration were measured by use of 3 clot-detection assay systems (2 mechanical and 1 photo-optic). Factor VIII and factor IX coagulant activities (FVIII:C and FIX:C, respectively) were determined by use of a manual tilt-tube method and a mechanical clot-detection device. RESULTS: Significant differences were not detected in median PT, fibrinogen concentration, FVIII:C, or FIX:C between 3.2 and 3.8% citrate for any assay system. A significant prolongation in aPTT for 3.2% citrate, compared with 3.8% citrate, was found in 1 mechanical system. CONCLUSIONS AND CLINICAL RELEVANCE: Citrate concentration does not significantly affect results of most coagulation assays, regardless of assay system. The aPTT was mildly influenced by the citrate concentration, although this was animal-, instrument-, and reagent-dependent. The choice of 3.2 or 3.8% citrate as an anticoagulant for coagulation tests has minimal influence on assay results in healthy dogs or dogs with hereditary hemostatic disorders.

Animals↗
PubMed2001

Preliminary characteristics of the prothrombin converting enzyme from venom of Stephen's banded snake (Hoplocephalus stephensii).

Stephen's banded snake (Hoplocephalus stephensii) is an infrequently encountered Australian elapid species. The crude venom contains coagulant activity and the component responsible is a prothrombin activator requiring factor V for activity. SDS-PAGE of the isolated native protein revealed two bands at 23 and 36 kDa. These findings indicate that the procoagulant is similar to that found in the Australian tiger snake (Notechis scutatus) and thus resembles factor Xa.

Animals↗
PubMed2004

Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias.

A North American registry for rare bleeding disorders [factor (F)II, factor (F)VII, factor (F)X, factor (F)V, factor (F)XIII, fibrinogen deficiencies and dysfibrinogenemias] was established to gather information about disease prevalence, genotyping frequency, diagnostic events, clinical manifestations, treatment and prophylaxis strategies, as well as disease- and treatment-related complications. Questionnaires were sent to 225 hemophilia treatment centers in the USA and Canada. Among 26% of responding centers, 294 individuals [4.4% of the registered children (200/4583) and 2.4% of adults (94/3809)] were diagnosed with one or more of the rare bleeding disorders (RBDs) included in this survey. The ethnic distribution for each disorder paralleled that of the general US population with the exception of the disproportionately large number of Latinos with FII deficiency. Only 5.4% of affected individuals were genotyped. An abnormal preoperative bleeding screen most often led to diagnosis. The most common coagulopathy was FVII deficiency; however, 40% of homozygous patients were asymptomatic. FX and FXIII deficiencies caused the most severe bleeding manifestations. Among all RBDs, the most common sites of bleeding were skin and mucus membranes. Multiple products were used to treat hemorrhage; however, half of the bleeding episodes required no therapy. The majority of patients suffered no long-term complications from hemorrhage. Treatment-related complications included viral seroconversion, anemia, allergic reactions and venous access device-related events. This registry provides the most comprehensive information to date about North American individuals with RBDs and could serve as an important resource for both basic scientist and clinician.

Adolescent↗
PubMed2004

Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders.

Combined deficiency of factor (F)V and FVIII (F5F8D) and combined deficiency of vitamin K-dependent clotting factors (VKCFD) comprise the vast majority of reported cases of familial multiple coagulation factor deficiencies. Recently, significant progress has been made in understanding the molecular mechanisms underlying these disorders. F5F8D is caused by mutations in two different genes (LMAN1 and MCFD2) that encode components of a stable protein complex. This complex is localized to the secretory pathway of the cell and likely functions in transporting newly synthesized FV and FVIII, and perhaps other proteins, from the ER to the Golgi. VKCFD is either caused by mutations in the gamma-carboxylase gene or in a recently identified gene encoding the vitamin K epoxide reductase. These two proteins are essential components of the vitamin K dependent carboxylation reaction. Deficiency in either protein leads to under-carboxylation and reduced activities of all the vitamin K-dependent coagulation factors, as well as several other proteins. The multiple coagulation factor deficiencies provide a notable example of important basic biological insight gained through the study of rare human diseases.

Carbon-Carbon Ligases↗
PubMed1998

Performance characteristics of a new synthetic APTT reagent.

Performance characteristics of a totally synthetic activated partial thromboplastin time (APTT) reagent, recently available commercially, were evaluated and compared with a rabbit-brain extracted reagent. We found that the synthetic reagent, Synthasil, returned significantly higher normal APTT values than the brain-extracted reagent, Thrombosil. APTT ratios (APTT patients/normal mean APTT), yielded by Synthasil were higher in the majority of patients receiving heparin therapy. Synthasil also returned longer APTT values than did Thrombosil on normal plasma spiked with heparin. On patients with lupus anticoagulants, APTTs assayed with Synthasil were generally longer than with Thrombosil. However, the differences disappeared when APTT values were converted to ratios. Factors XII-, XI-, IX- and VIII-deficient plasmas supplemented with normal plasma to yield activities of 2-50%, generally gave longer APTTs with Synthasil than with Thrombosil. However, this was not always the case on plasmas from haemophilias A and B patients. No reduction in Synthasil activity was noted after the reagent had been left at 24 degrees C for 28 days.

Coagulation Protein Disorders↗
PubMed2002

Rare coagulation deficiencies.

UNLABELLED: Deficiencies of coagulation factors (other than factor VIII and factor IX) that cause a bleeding disorder are inherited as autosomal recessive traits and are generally rare, with prevalences in the general population varying between 1 : 500 000 and 1 : 2 000 000. In the last few years, the number of patients with recessively transmitted coagulation deficiencies has increased in European countries with a high rate of immigration of Islamic populations, because in these populations, consanguineous marriages are frequent. Owing to the relative rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects and the actual management of bleeding episodes are not as well established as for haemophilia A and B. This article reviews these disorders in terms of their clinical manifestations and characterization of the molecular defects involved. The general principles of management are also discussed. KEYWORDS: afibrinogenaemia, autosomal recessive disorders, factor VIII, factor XI, factor XIII.

Blood Coagulation Factors↗
PubMed2003

The use of recombinant factor VIIa in children with inherited platelet function disorders.

Inherited deficiencies of platelet surface glycoproteins such as Glanzmann's thrombasthenia (GT) or Bernard-Soulier syndrome (BSS) can lead to a severe bleeding diathesis. In the past, bleeding episodes in these patients have often required platelet transfusion to secure haemostasis but recently a number of patient reports have suggested that recombinant factor VIIa (rVIIa) may also be effective. We have used rVIIa on 33 occasions in seven children with inherited platelet function disorders over a 2-year period: five had GT, one had BSS and one had storage pool disease with a severe phenotype. Bleeding ceased with rVIIa alone in 10 of 28 acute bleeding episodes, but recurred in two of these. The two features that predicted response to rVIIa were the severity of the bleeding and the delay from the onset of bleeding to treatment. Five episodes of planned surgical intervention were treated successfully with rVIIa. Eighteen out of the 28 acute episodes and none of the planned surgical episodes required blood product support. We have found variable efficacy of rVIIa for acute bleeding episodes in this small series of children with inherited platelet function defects but larger studies are warranted, particularly as rVIIa is a relatively low-risk treatment approach for these disorders.

Acute Disease↗
PubMed2004

Whole blood clot formation phenotypes in hemophilia A and rare coagulation disorders. Patterns of response to recombinant factor VIIa.

Until now, no routinely used clotting assay has demonstrated the power to reflect significantly a patient's response to recombinant factor (rF)VIIa. Adopting a thrombelastographic principle, profiles of continuous whole blood (WB) coagulation were studied in minimally altered WB activated with a small amount of tissue factor (TF). Investigation of the WB clotting profile was performed before and after ex vivo addition of rFVIIa 20 nm to WB from 26 patients with hemophilia A, two patients with severe hemophilia B, and individuals with deficiencies of FV, FX, FXI, and FXIII. In five patients with hemophilia plus inhibitors, the response to ex vivo added rFVIIa and to activated complex concentrate (APCC) was studied. Patients with severe and moderate hemophilia A demonstrated remarkable variance in the hemostatic characteristics at baseline, even in groups with the same FVIII:C activity levels. The response to rFVIIa at 20 nm also varied extensively, the effect correlating with the continuous WB coagulation phenotype at baseline. This indicates that the efficacy of rFVIIa may be optimized by tailoring the dose according to the hemostatic response to varying doses tested prior to in vivo administration. In patients with inhibitors against FVIII and factor IX, rFVIIa and APCC substitution resulted in quite similar response patterns that appeared to be dose dependent. In severe FV, FX, and FXIII-deficient WB, rFVIIa addition induced minor changes only. In FXI deficiency, rFVIIa normalized the dynamic properties of clotting, although a reduced clot firmness remained unchanged. In conclusion, the thrombelastographic analysis of WB clotting, as activated with a minute amount of TF, seems an interesting method that detects phenotypic variation amongst hemophilia patients. The method appears useful for assessment of the hemostatic capacity and it seems a promising tool for evaluation of the individual response to rFVIIa or APCC before and during in vivo administration.

Adult↗
PubMed2006

Inherited thrombophilia.

Inherited thrombophilia can be defined as a genetically determined predisposition to the development of thromboembolic complications. Since the discovery of activated protein C resistance in 1993, several additional disorders have been described and, at present, it is possible to identify an inherited predisposition in about 60 to 70% of patients with such complications. These inherited prothrombotic risk factors include qualitative or quantitative defects of coagulation factor inhibitors, increased levels or function of coagulation factors, defects of the fibrinolytic system, altered platelet function, and hyperhomocysteinemia. In this review, the main inherited prothrombotic risk factors are analyzed from epidemiological, laboratory, clinical, and therapeutic points of view. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in particular conditions such as childhood and pregnancy.

Afibrinogenemia↗
PubMed2006

Acquired von Willebrand syndrome: an underdiagnosed and misdiagnosed bleeding complication in patients with lymphoproliferative and myeloproliferative disorders.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease (VWD). Unlike the congenital disease, AVWS usually occurs in individuals with no personal or family history of bleeding. The prevalence of AVWS in the general population is unknown because data from large prospective studies of this syndrome are not available. Although AVWS is particularly frequent in lymphoproliferative or myeloproliferative disorders, it can also be associated with solid tumors, immunologic and cardiovascular disorders, and other miscellaneous conditions. Diagnosis of AVWS is based on assays measuring the activity of von Willebrand factor (VWF). This tends to be abnormally low, but factor VIII (FVIII) coagulant activity can sometimes be normal. FVIII/VWF inhibiting activity is found in only a minority of cases. Bleeding episodes in patients with AVWS are mostly of the mucocutaneous type and can be managed with desmopressin, plasma-derived FVIII/VWF concentrates, and intravenous immunoglobulin (IVIg). Recombinant activated factor VII can be useful in patients unresponsive to standard therapy. An updated version of the International Registry on AVWS, recently available online, will provide more information on this rare, but underdiagnosed and misdiagnosed, disorder.

Adolescent↗
PubMed2002

Thrombophilic markers in patients with congenital bleeding disorders.

We have studied the presence or absence of thrombophilic markers in 59 patients with congenital bleeding disorders. Theoretically, the coexistence of coagulation factor deficiency and thrombophilia in patients with haemophilia may cause the bleeding tendency to decline. In 8 cases we have found thrombophilic marker positivity, in 7 patients APC resistance and in 1 patient protein S deficiency has been revealed. The presence of thrombophilic markers did not affect the frequency of bleeding episodes or the development of haemophilic arthropathy. The factor concentrate utilization, however, was lower in the group carrying thrombophilic markers, which indicates that the bleeding episodes were less severe. Relying on the strength of these findings, the medicinal influencing of inhibitor mechanisms may present itself as a potential therapy.

Activated Protein C Resistance↗