Characteristics of Rare Coagulation Factors Deficiency in Adults, an Experience from Qatar

Background

Rare factors (F) deficiencies are defined as deficiencies of factors other than F VIII or IX. They are inherited as autosomal recessive with a prevalence that varies between 1:500,000 to 1:2000,000.FI deficiency includes Afibrinogenemia, Hypofibrinogenemia and Dysfibrinogenemia. While most patients with dysfibrinogenemia don't bleed patients with afibrinogenemia can present with life threatening bleeding. FII deficiency can be acquired or inherited. the most frequent severe symptoms are muscle hematomas and hemarthrosis.

With FV deficiency some patients may be asymptomatic while children with severe deficiency can present with CNS bleeding. Patients with low FV should also get their FVIII checked to rule out combined (F5F8) deficiency which is a separate rare coagulation disorder that results from a mutation in a protein that transfers both factors from the cell to the blood stream. Symptoms are generally mild and it rarely causes hematomas or hemarthrosis.

FVII deficiency is the most common autosomal recessive coagulation disorder (1:500,000). The severity of symptoms is reported to be poorly correlated with the plasma levels.

FX deficiency can present with serious bleeding manifestations. Options for treatment include fresh frozen plasma (FFP) or prothrombin concentrate.

FXI deficiency (Hemophilia C) unlike F8 and F9 doesn't cause joint or muscle bleeding. Hemophilia C is the second most common bleeding disorder affecting women following Von Willebrand disease.

The most common presentation of FXII deficiency is asymptomatic prolongation of aPTT. Deficiency of this factor carries a more thrombotic risk rather than bleeding because it plays a bigger role in initiation of fibrinolysis compare to its contribution to the coagulation cascade.

Most patients with FXIII deficiency experience symptoms from birth often bleeding from the umbilical cord stump and bleeding symptoms tend to continue throughout life.

Methodology

Data was collected from hematology outpatients' clinics from January 2018 to June 2020. Patients above 18 years with rare factor deficiencies.were included in the study,We excluded FVIII and IX as it is less rare and there are specific guidelines for these patients.Data included were demographics, the factor deficient, level, surgical history and others.

Results

The total number is 29 patients. The mean age is 34 years (18-77). There is female predominance with 69 %. 65 % of the patients were Qataris and 36% from other nationalities. The most deficient factor is FI 41%, followed by FVII 20 %, then FXII and XIII. Interestingly we found one rare case of combined F5F8 deficiency in a Lebanese lady. Family history was positive in 41 % of cases, almost in all the cases of Fibrinogen deficiency.

All the cases of Hypofibrinogenemia came from one qatari Tribe.

38 % of the patients had history of bleeding, while 80 % had surgical procedures. 55% received replacement therapy for bleeding or before procedures. Due to the history of transfusions we checked for HIV, HBV and HCV status and we found only one case with HCV.

Conclusion

Some factor deficiencies pose a challenge in hematology clinics due its rarity and lack of guidelines. Mild deficiency can be discovered for the first time in adult life, during surgery, pregnancy or gynecological procedures. Therefore, females are more likely to be discovered than males. Abnormalities in coagulation should be considered before surgical procedures, which might require hematologist consultation.

Educating patients and physicians will help in preparing these patients and initiation of protocols if needed.

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