Combined Deficiency Of Factor Research Articles

Combined deficiency of factors II, VII, IX, and X (Borgschulte-Grigsby deficiency) in pregnancy

Background: Combined deficiency of vitamin K–dependent coagulation factors (II, VII, IX, X) is an uncommon challenge for the expectant gravida. Case: A 34-year-old primigravida had congenital combined deficiency of factors II, VII, IX, and X that were incompletely sensitive to vitamin K. She had an altered form of vitamin K–dependent factors that retained immunologic activity but lacked coagulant activity and the normal complement of gamma-carboxyglutamic acid residues. She required vitamin K supplementation throughout her life. After an uneventful pregnancy she had postpartum hemorrhage resulting from an episiotomy. Fresh frozen plasma was administered to achieve hemostasis. The remainder of her postpartum course was normal. Conclusion: Combined congenital deficiency of factors II, VII, IX, and X can be managed in pregnancy with the use of vitamin K and fresh frozen plasma.

COMBINED DEFICIENCY OF FACTORS II, VII, IX, AND X (BORGSCHULTE-GRIGSBY DEFICIENCY) IN PREGNANCY

In Brief Background Combined deficiency of vitamin K–dependent coagulation factors (II, VII, IX, X) is an uncommon challenge for the expectant gravida. Case A 34-year-old primigravida had congenital combined deficiency of factors II, VII, IX, and X that were incompletely sensitive to vitamin K. She had an altered form of vitamin K–dependent factors that retained immunologic activity but lacked coagulant activity and the normal complement of gamma-carboxyglutamic acid residues. She required vitamin K supplementation throughout her life. After an uneventful pregnancy she had postpartum hemorrhage resulting from an episiotomy. Fresh frozen plasma was administered to achieve hemostasis. The remainder of her postpartum course was normal. Conclusion Combined congenital deficiency of factors II, VII, IX, and X can be managed in pregnancy with the use of vitamin K and fresh frozen plasma. Vitamin K and fresh frozen plasma are essential in the treatment of pregnant women with deficiencies of vitamin K–dependent factors (II, VII, IX, X).

76-Year-Old Man With Retroperitoneal Bleeding After Prostatectomy

76-Year-Old Man With Retroperitoneal Bleeding After Prostatectomy

Acquired haemophilia A

The distinction between a specific factor inactivator and a non-specific inhibitor is important when confronted by a patient with a history of bleeding and abnormal in-vitro coagulation tests. We report on two patients who presented with bleeding and a prolonged activated partial thromboplastin time. Initial factor assays suggested combined deficiency of factors VIII and IX as a result of the presence of inactivators. The use of dilution studies, chromogenic assays, a novel in-house enzyme-linked-immunosorbent-assay-based technique and phospholipid neutralization, demonstrated that Case 1 had a genuine factor VIII inactivator resulting in factor VIII levels of less than 1 IU/dl but no factor IX deficiency. Case 2 had normal levels of factor VIII on further testing and no specific inactivator to either factor VIII or IX but a potent antiphospholipid antibody which had interfered with the phospholipid-dependent in-vitro assays. Care must be taken in the interpretation of laboratory assays in the presence of antiphospholipid antibodies to ensure that the correct diagnosis is made and inappropriate treatment avoided.

Bleeding symptoms in 27 Iranian patients with the combined deficiency of factor V and factor VIII.

Inherited deficiency of factors V and VIII is the most frequent combined coagulation defect. The cases reported so fair are mostly single cases or small series from different centres, making it difficult to evaluate the overall pattern of clinical manifestations of the combined defect. We examined at a single institution 27 Iranian patients. Mucocutaneous and post-surgical bleeding were the most frequent clinical manifestations. The presence of two defects did not make the severity of bleeding greater than that expected in patients with single coagulation defects of similar degrees.

Congenital combined deficiency of factor V and factor VIII with acquired ichthyosis, epidermodysplasia verruciformis, and immunological abnormalities

Congenital combined deficiency of factor V and factor VIII with acquired ichthyosis, epidermodysplasia verruciformis, and immunological abnormalities

A combined deficiency of factor VIII and contact activation defect in a family of cats

The coagulation parameters of a litter of kittens born to an obligate carrier of haemophilia A (classical haemophilia, factor VIII deficiency) are described. Three of four kittens were found to have an intrinsic coagulation defect, but only one was haemophilic. Factor XII deficiency was confirmed in one female, the other female and the dam being carriers of the defect. A confirmed haemophilic male from a previous litter was also found to be a factor XII deficient carrier.

Response of Protein C and Protein C inhibitor to warfarin therapy in patient with combined deficiency of factors V and VIII

The role of Protein C in combined factor V/VIII deficiency was examined by reducing the Protein C concentration using warfarin therapy in a patient with the combined deficiency. The factor VIII deficiency was like Hemophilia-A, with deficiency of VIII:C and VIII:C(Ag), but normal VIIIR:Ag and VIIIR:cof. The factor V deficiency was due to loss of the V antigen. During warfarin therapy the Protein C level was reduced, but concentrations of factors V and VIII did not change. Protein C Inhibitor was normal throughout. Thus combined factor V/VIII deficiency is not related to Protein C levels.

Normal titer of functional and immunoreactive protein-C inhibitor in plasma of patients with congenital combined deficiency of factor V and factor VIII

Protein-C inhibitor (PCI) is a newly described plasma inhibitor directed against a vitamin-K-dependent serine protease, activated protein-C, which is involved in the inactivation of factor V and factor VIII. Marlar and Griffin have reported that PCI activity is absent in the plasma of patients with congenital combined factor V/VIII deficiency. We have measured the levels of PCI in the plasma of seven unrelated patients with this disorder using both functional and immunologic methods. The rate at which the amidolytic activity of activated protein-C was neutralized in the patients' plasma was essentially identical to that observed in normal plasma. The titer of PCI antigen, as measured by an electroimmunoassay using a monospecific anti-PCI serum, was 5.3 +/- 1.6 micrograms/ml in the patients' plasma and was not significantly different from that of normal plasma (5.3 +/- 2.7 micrograms/ml, n = 30). The levels of factor-V-related antigen, factor V coagulant antigen, and factor VIII coagulant antigen were low in all patient plasma and were in good agreement with their respective coagulant activity. Our results do not appear to support the hypothesis that combined factor V/VIII defect is due to a lack of PCI.

Combined deficiency of factor V and factor VIII: report of a family and genetic analysis.

Summary. A family, in which the combined deficiency of factor V and factor VIII is segregating, is described. It is the first family reported which was detected through routine coagulation studies and the first one in which paternal relatives are found to be affected as well as maternal relatives. Over 40 family members have been studied. A review of the genetic hypotheses in the literature is presented. The data from this family and from the previously reported ones are analysed as to the mode of inheritance. An autosomal recessive mode of inheritance with a marked degree of penetrance (27.2–72.8%) and varying expressivity in heterozygotes seems to be the most likely explanation. The aims for further studies are outlined.

Combined factor-V and factor-VIII deficiency: report of four cases.

Summary:Three sisters, descendants of a consanguineous marriage, with combined Factor‐V and Factor‐ VIII deficiency, enuresis until early adulthood, and psychopathological manifestations have been reported. The family study, which included three generations, revealed several clinical and laboratory patterns: mild bleeding with normal levels of Factors V and VIII; mild bleeding with mild deficiencies of Factors V and VIII, mild Factor‐V and Factor‐VIII deficiencies without bleeding; neither bleeding nor blood clotting abnormalities. The mode of inheritance of the combined deficiency of Factors V and VIII seemed to be autosomal with complete expression in the homozygous state and partial or no expression in the heterozygous state. This conclusion is in accordance with previous reports. The association of the blood coagulation defect with psychopathological manifestations and enuresis in the present kindred appeared coincidental.A fourth woman with similar clotting defects but with normal personality is reported from another family. Her parents were also related.Infusion of fresh haemophilia A plasma to one of the patients in the first family had no effect on Factor‐V and Factor‐VIII levels, but physical effort had a remarkable effect, the levels rising after 24 hours from 16 per cent to 41 per cent and from 0.7 per cent to 32 per cent respectively. In the patient from the other family, only the Factor VIII rose after exercise (from 2.3 to 18.8 per cent), but there was a similar delay in the response.The technical assistance of Mrs. E. Goldberg is gratefully acknowledged. We are also grateful to Dr. J. Caen for plasma from a known case of Factor‐VII deficiency.

Congenital Combined Deficiency of Factor V and Factor VIII

SummaryA case of congenital combined deficiency of factor V and factor VIII was reported. The patient, a 9 year old boy, gave a history of epistaxis, hematomas, and of hemorrhages following dental extraction since the age of 2 ; plasma levels of factor V and factor VIII were found to be 16% and 8% of normal, respectively. No one in his family had a deficiency of either factor. The effects of transfusion of normal fresh plasma and whole blood from a patient with hemophilia A were studied. While the former were similar to the pattern as seen in classical hemophilia, the latter consisted of an immediate increase of factor V activity and a delayed increase of factor VIII activity, despite the fact that factor VIII activity was almost absent from the donor’s blood.

The Treatment of Patients with Factor-V Deficiency

Two patients with congenital factor-V deficiency and a third with a combined deficiency of factor V and factor VIII are described. Under cover of fresh frozen plasma, tooth extractions were performed on two of these patients and spontaneous bleeding arrested. It is concluded that the achievement of a blood level of factor V of 20 per cent once daily is sufficient to assure adequate haemostasis. A low recovery of factor V activity in the plasma following infusion was found. However, in spite of this, adequate blood levels were easily attained due to the excellent preservation of factor V activity in the stored fresh frozen plasma.