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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2019  |  Volume : 30  |  Issue : 5  |  Page : 1171-1174
Congenital factor VII deficiency presenting first time as isolated recurrent hematuria at late age


1 Department of Nephrology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Plastic Surgery, Fortis Hospital, Ludhiana, Punjab, India

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Date of Submission12-Oct-2018
Date of Acceptance18-Nov-2018
Date of Web Publication4-Nov-2019
 

   Abstract 


Hematological conditions rarely present as isolated hematuria. Factor VII deficiency is a rare congenital coagulopathy inherited as autosomal recessive pattern. It usually presents a severe life-threatening bleeding at an early age. The presentation of congenital factor VII factor deficiency for the first time as recurrent hematuria at a later age is a rare presentation. We report a case of a 23-year-old male, who presented to us with recurrent episodes of painless hematuria for the past three months due to congenital factor VII deficiency.

How to cite this article:
Sethi S, Mehta S, Sethi N, Makkar V, Kaur S, Jhingar MK. Congenital factor VII deficiency presenting first time as isolated recurrent hematuria at late age. Saudi J Kidney Dis Transpl 2019;30:1171-4

How to cite this URL:
Sethi S, Mehta S, Sethi N, Makkar V, Kaur S, Jhingar MK. Congenital factor VII deficiency presenting first time as isolated recurrent hematuria at late age. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Nov 20];30:1171-4. Available from: http://www.sjkdt.org/text.asp?2019/30/5/1171/270276



   Introduction Top


Hematological conditions can present as hematuria, although the incidence is rare. Isolated presentation of hematuria is even rarer as these bleeding disorders are accompanied by bleeding at other sites. Factor VII deficiency is a rare congenital coagulopathy inherited as autosomal recessive hemorrhagic disorder with an incidence of one in 500,000 population.[1] Prolonged prothrombin time (PT) with normal partial thromboplastin time indicates factor VII deficiency. Factor VII is a Vitamin K-dependent coagulation factor synthesized in the liver and has a short circulating half-life of 3–4 h. For the definitive diagnosis, the specific factor VII level should be investigated. Clinical bleeding can vary widely and does not always correlate with the level of factor VII coagulant activity measured in plasma. Mortality is related to severe bleeding, most often resulting from central nervous system (CNS) hemorrhage. Most severe cases of factor VII deficiency are diagnosed during childhood, often during the first six months of life. In infancy, the most common bleeds occur in the gastrointestinal tract or CNS, accounting for 60%–70% of bleeds in this age group.[2],[3] However, patients with mild deficiency remain unnoticed or present at a later age, as in the index case. The presentation of congenital factor VII factor deficiency for the first time as isolated recurrent hematuria at later age is a rare presentation, not reported previously in literature.


   Case Report Top


Informed consent was obtained from the patient before presenting the report.

A 23-year-old male born of nonconsan-guineous marriage with normal birth and development history was admitted to us for the evaluation of recurrent gross hematuria without clots. The patient had recurrent episodes of painless hematuria off and on for the past three months. There was no history of any febrile illness preceding these episodes. He had no history of rash, oral ulceration, photosensitivity or any constitutional symptoms such as loss of weight or appetite. There was no history of diabetic mellitus, hypertension, renal stone disease or any other systemic illness or history of drug intake including any anticoagulant medication. There was neither history of bruise formation after trivial trauma in the past nor was there family history of any bleeding disorder. On examination, he was hemodynamically stable. The systematic examination was unremarkable. Full blood count showed hemoglobin of 10.6 g/dL, total leukocyte count of 5700 (differential leukocyte count: N 52%, L 40%, M 4%, E 2%, B 2%), platelet count of 2.48 lakh, blood urea of 22 mg/dL, serum creatinine of 0.7 mg/dL, serum protein of 8.9 mg/dL, albumin of 4.2 mg/dL, sodium of 137 mmol/L, potassium of 4.5 mmol/L, total bilirubin of 0.39 mg/dL, direct 0.2 mg/dL, alanine aminotransaminase of 15 U/L, aspartate aminotransaminase of 9 U/L, alkaline phosphatase of 101 U/L, calcium of 8.5 mg/dL, phosphorus of 3.9 mg/dL, and uric acid of 5.1 mg/dL. The anti-nuclear antibody was negative by immunofluorescence, viral markers were nonreactive and thyroid profile and complement levels were normal. Urinalysis revealed significant hematuria with plenty of red blood cells (RBCs) with no RBC casts or any evidence of dysmorphic RBCs; there was no proteinuria. The spot urine protein-creatinine ratio was 0.2. Bleeding time, clotting time, urine culture, and urine for malignant cytology were unremarkable. The patient’s PT was elevated to 68.4 with the international normalized ratio of 6.16. His activated partial thromboplastin time (APTT), D dimer, fibrinogen, and fibrin degradation products were normal. Further investigations revealed that the PT could be corrected with normal plasma, suggesting an inherent clotting factor deficiency. Ultrasound and contrast computed tomography scan of the abdomen showed no calculus or mass lesions. His renal biopsy was planned, but could not be done in view of deranged PT. A cystoscopy performed after transfusion of fresh frozen plasma did not reveal any abnormality. Clotting factor assay (i.e., factor VII activity) was suggestive of factor VII deficiency with levels of 8.3% (normal range 70–120). Factor VII assays of both parents, however, showed normal levels. The literature was also searched for similar case findings, but this was one of the rare presentations of congenital factor VII deficiency, presenting for the first time as isolated recurrent hematuria. The patient was discharged and is on regular follow-up.


   Discussion Top


Factor VII deficiency is a rare congenital blood disorder, inherited in an incomplete autosomal recessive pattern. Factor VII is essential for the activation of coagulation in the extrinsic pathway. Its concentration within the plasma is very low, and of all the classical coagulation factors, factor VII has the shortest half-life of only 3–4 h. Factor VII deficiency was first described by Alexander et al.[4] Only few cases[5] have been reported from India. Type 1 deficiencies result from decreased biosynthesis or accelerated clearance; Type 2 abnormalities represent a dysfunctional molecule. More than 100 mutations, mostly missense mutations,[6],[7] have been identified in the factor VII gene located on chromosome 13. Frequency is higher in countries where consanguineous marriage is more common. Consanguinity is an important element in diseases with an autosomal recessive inheritance. However, in the series of 75 patients reviewed by Ragni et al, only 19% were reported to be consanguineous.[8] In our patient, both parents were nonconsanguinous and there was no significant family history of bleeding tendencies. Although their factor VII levels were normal, this condition is known to have a rather variable expression with poor correlation between reported coagulant activity and clinical bleeding tendency. This may well be the explanation for the normal factor VII assay in the parents. Another possibility is that the parents are gonadal mosaics or alternatively, only one of them is a gonadal mosaic with the other mutation occurring spontaneously in the patient himself. Acquired factor VII deficiency may arise due to Vitamin K deficiency, Vitamin K antagonist therapy or liver disease. In these conditions, reduced factor VII levels are associated with reduced levels of other Vitamin K-dependent factors. Acquired factor VII deficiency[9],[10] is far more common than inherited deficiency. In the index case, other factor assays in blood were found to be normal. The PT is prolonged in factor VII deficiency and the INR is elevated. The aPTT is within the reference range in isolated factor VII deficiency as seen in the index case. Factor VII assays are performed by using thrombo-plastin-dependent one-stage clotting assay. The more sensitive thromboplastins, usually recombinant human thromboplastin, are preferred for measuring factor VII activity in the very low range. As with the hemophilia group, factor VII deficiency may be classified into the severe form (factor VIIc <1%) and the mild-to-moderate form (Factor VIIc 5%–7%)[11] However, the plasma level of factor VII that is required for hemostasis is not known and this perhaps contributes to its rather variable expression and poor correlation between reported coagulant activity and clinical bleeding tendency.[6],[8]

Management of acute hemorrhage primarily consists of FVII replacement therapy to treat bleeding.[2],[3] Levels of more than 10% are usually hemostatic, although higher levels may be advisable in the event of a severe bleeding episode. Because factor VII has a short halflife (3–4 h), repeat treatment may be necessary in all, except minor bleeding episodes. Treatment alternatives include fresh frozen plasma, which is least effective because of the volume required to provide adequate factor VII replacement. Prothrombin complex concentrates contain factors II, IX, and X in addition to factor VII. These agents carry a risk of thrombogenic complications, particularly with repeated administration. If available, factor VII concentrates are preferred over untreated plasma. Recombinant activated factor VII was originally developed to treat patients with hemophilia with factor inhibitors. It can be used at lower doses for patients with congenital FVII deficiency. Maintaining factor VII levels of at least 15%–25% provides adequate hemostasis levels for most surgical procedures.

In conclusion, the presentation of congenital factor VII factor deficiency for the first time as isolated recurrent hematuria at a later age is a rare occurrence. Prolonged PT with normal partial thromboplastin time indicates factor VII deficiency. For the definitive diagnosis, the specific factor VII level should be investigated. Management consists of factor VII replacement therapy to treat active bleeding.

Conflict of interest: None declared.



 
   References Top

1.
Roberts SR, Escobar MA. Less common congenital disorders of hemostasis. In: kitchens CS, Alving BM, Kessler CM, editors. Cummulative Hemostasis and Thrombosis. Philadelphia: w. B. Saunders Company; 2002.  Back to cited text no. 1
    
2.
Mariani G, Dolce A, Marchetti G, Bernardi F. Clinical picture and management of congenital factor VII deficiency. Haemophilia 2004:10 Suppl 4:180-3.  Back to cited text no. 2
    
3.
Ingerslev J, Kristensen HL. Clinical picture and treatment strategies in factor VII deficiency. Haemophilia 1998:4:689-96.  Back to cited text no. 3
    
4.
Alexander B, Goldstein R, Landwehr G, Cook CD. Congenital SPCA deficiency: A hitherto unrecognized coagulation defect with hemorrhage rectified by serum and serum fractions. J Clin Invest 1951:30:596-608.  Back to cited text no. 4
    
5.
Sanghvi JP, Muranjan MN, Bavdekar SB, Parmar RC. Congenital factor VII deficiency. Indian J Pediatr 2004:71:441-3.  Back to cited text no. 5
    
6.
Cooper DN, Millar DS, Wacey A, Banner DW, Tuddenham EG. Inherited factor VII deficiency: Molecular genetics and pathophysiology. Thromb Haemost 1997;78:151-60.  Back to cited text no. 6
    
7.
Mariani G, Lo Coco L, Bernardi F, Pinotti M. Molecular and clinical aspects of factor VII deficiency. Blood Coagul Fibrinolysis 1998:9 Suppl 1:S83-8.  Back to cited text no. 7
    
8.
Ragni MV, Lewis JH, Spero JA, Hasiba U. Factor VII deficiency. Am J Hematol 1981:10:79-88.  Back to cited text no. 8
    
9.
Biron C, Bengier C, Gris JC, Schved JF. Acquired isolated factor VII deficiency during sepsis. Haemostasis 1997:27:51-6.  Back to cited text no. 9
    
10.
Granger J, Gidvani VK. Acquired factor VII deficiency associated with Wilms tumor. Pediatr Blood Cancer 2009:52:394-5.  Back to cited text no. 10
    
11.
Mariani G, Testa MG, Di Paolantonio τ, Molskov Bech R, Hedner U. Use of recorn-binant, activated factor VII in the treatment of congenital factor VII deficiencies. Vox Sang 1999:77:131-6.  Back to cited text no. 11
    

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Correspondence Address:
Sudhir Mehta
Department of Nephrology, Dayanand Medical College and Hospital, Ludhiana, Punjab
India
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DOI: 10.4103/1319-2442.270276

PMID: 31696859

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    Abstract
   Introduction
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    References
 

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