Factor VII deficiency is an uncommon genetic disorder. In order for blood to clot normally, clotting factors, which are specialised proteins, are required. Chronic, uncontrolled bleeding episodes can occur in people with factor VII deficiency. It depends largely on the individual how severe their factor VII insufficiency is. It is usually considered to be associated with bleeding only in the severely affected subject and heterozygotes (>10%) are not considered at risk [1]. Some people may be asymptomatic (without symptoms), while others may start to experience minor, moderate, or even severe issues that could be fatal as early as infancy. Factor VII deficiency is caused by mutations of the F7 gene and is inherited as an autosomal recessive disorder [2]. Factor VII deficiency was first described in the medical literature by Alexander et al. and was referred to as prothrombin conversion accelerator deficiency. The disorder has also been known as Alexander’s disease. This disorder can also be acquired during lifetime. 

Case Report

A 40year old male came with c/o pain in left hip with change in gait since 6 months. The pain was dull aching with insidious in onset and gradual in progression. After examining and investigating he was diagnosed with avascular necrosis of left femoral head. Patient was admitted in ortho ward and was planned for total hip replacement surgery. Patient was sent for pre-anesthetic checkup in the OPD. Patient was not having any comorbidities and no bleeding tendency. Patient was hospitalised in December 2021 i/v/o megaloblastic anaemia and Hb of 3.7 gm%; however, after receiving blood, Hb improved to 7.3 gm%. After few months, patient was planned for total hip replacement, but on routine investigations he showed persistently raised INR. Hence, he underwent evaluation. He was screened for APLA and HPLC, which was insignificant. Pt was treated with inj. Vit K, discharged with INR 1.21 and advised for follow-up in orthopedics OPD. At present, on General Examination, patient was Conscious oriented, averagely built with wt- 60kg and ht-170 cm, HR-70/min, NIBP-130/80 mm of Hg, SpO2-99% on room air. Mallampatti classification II with normal TMJ and neck movement. No significant Cardiorespiratory findings. Routine preoperative investigations including CBC, KFT, RBS, ECG were advised along with PT/INR and aPTT as patient had past history of prolonged PT/INR. On investigations, CBC showed Hb – 7.3 gm% and platelet-96,000, KFT and electrolytes- creatinine 0.99, urea 22, sodium 136, potassium 5.25, PT/INR-19.6/1.66, APTT-35.8. Viral markers were negative. Blood group- O Rh Positive, ECG and CXR were WNL. Preoperatively patient was treated with FFP and Inj. Vit K for PT/INR correction and whole blood was transfused for anemia correction. INR was persistently on higher side inspite of the ongoing treatment while the aPTT was normal. Hence, the mixing study was done. Patient tested negative for factor inhibitors. The differential diagnosis included Vitamin K deficiency, liver disease, warfarin and DIC. As patient was not having any of the above, our diagnosis inclined towards factor VII deficiency and hence we decided to investigate for levels of factor VII. It was 29.10% in our patient. Use the "Insert Citation" button to add citations to this document. 

About 0.25mg 12 hours before surgery. Patient was kept NBM for 6 hours for solids and clear fluids were permitted until 2 hours prior to surgery. Written and informed consent was taken. Patient was taken inside the OT, multi-paramonitors attached including ECG, NIBP, pulseoxymeter. Two wide bore 16G and 18G intravenous access taken. INR on OT day was 1.6 and hence our plan of anaesthesia was general anaesthesia. Premedications given including inj. Ondansetron 4mg, inj. Glycopyrrolate 0.2mg, inj. Midazolam 1mg. Tranexamic acid 1gm and antibiotics given intravenously. Preoxygenation done using 100% oxygen for 5 minute and Induction started using inj. fentanyl and inj. propofol. Atracurium was given and airway was secured using cuffed endotracheal tube no. 8.5. Intubation went smooth and uneventful. Intraoperatively atracurium and fentanyl infusion started for analgesia and dexmedetomidine infusion for hemodynamic stability and hypotensive anaesthesia. Intraoperatively, the blood loss was around 800mL which exceeded the maximum allowable for that patient and hence the call was taken to transfuse FFP and blood. Dexmedetomidine infusion was stopped as there was hypotension and tachycardia. It was managed using phenylephrine. After receiving FFP the bleeding was under control and hemostasis was achieved. Total blood loss was about 2 liters and complete 2 points of PRC was given along with 4 FFP. At the end of the procedure patient was reversed using inj. Glycopyrrolate 0.5mg and inj. Neostigmine 2.5mg and extubation was smooth and uneventful. Before shifting patient was vitally stable and was not on any vasopressors support. Fentanyl patch of 25mcg/hr was used for postoperative analgesia. Post-operative Investigations were advised. Hb was 7.8gm%, INR was 1.44 and ABG was normal. Hence, one point of PRC was transfused. There was no significant bleeding from wound site.

This patient came to hospital for hip joint replacement and was incidentally found to have prolonged prothrombin time. He has no history of mucosal bleeding nor history of bleeding in joints or muscles, either spontaneously or following injury. No history suggestive of chronic liver disease, coagulopathy and use of warfarin, heparin or direct anticoagulants. DIC was also excluded from diagnosis following his investigations. His repeated work up shows prolonged PT and INR but normal aPTT. Only five disorders are associated with this picture. Inherited-factor 7 deficiency and Acquired- mild vitamin K deficiency, liver disease, warfarin or DIC. Deficient activity of coagulation factors in extrinsic pathway may be due to inherited disorders or acquired inhibitors for example autoantibodies. To rule out inhibitors mixing study was conducted in which the patient’s plasma is mixed with normal donor plasma. If the clotting occurs normally it indicates factor deficiency and if clotting doesn’t occur it indicates presence of factor inhibitor. Patient tested negative for inhibitors. And hence, we labelled it as factor VII deficiency. To assess the risk of bleeding in this asymptomatic patient during surgery we used ISTH-SSC bleeding assessment tool where overall score was zero [4]. His FVII:C level was 29.10% and it was observed in previous studies bleeding risk is extremely low in patients with FVII:C >10% [5]. Hence, patient and relatives were explained regarding the perioperative risks and informed and written consent was. Adequate blood and FFP was arranged for the surgery. Our plan of anaesthesia was hypotensive general anaesthesia. Neuraxial blockade was avoided considering the INR on higher side and looking at the associated risk of formation of hematoma. The procedure was done successfully.

In this patient, surgery was done under general anaesthesia and postoperative period was uneventful. Patients with factor VII deficiency usually remains undiagnosed unless they show any signs of bleeding or coagulatioanaesthesia, proper hemostasis and good postoperative n profiles are done. Hence, you need a careful evaluation during pre-anaesthetic checkup about any bleeding tendency [6,7] and preoperative preparations including arrangement of blood and fresh frozen plasma and also if possible factor VII depot preparation. Precautions should be taken regarding smooth induction and emergence from general analgesia.

1. Barnett, J.M. et al. “Lack of bleeding in patients with severe factor vii deficiency.” American Journal of Hematology, vol. 78, no. 2, February 2005, pp. 134–137. https://doi.org/10.1002/ajh.20262.

2. Cooper, D.N. et al. “Inherited factor vii deficiency: Molecular genetics and pathophysiology.” Thrombosis and Haemostasis, vol. 78, no. 1, July 1997, pp. 151–160.

3. Giansily-Blaizot, M. et al. “Inherited factor vii deficiency and surgery: Clinical data are the best criteria to predict the risk of bleeding.” British Journal of Haematology, vol. 117, no. 1, April 2002, pp. 172–175. https://doi.org/10.1046/j.1365-2141.2002.03408.x.

4. Rodeghiero, F. et al. “ISTH/SSC bleeding assessment tool: A standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders.” Journal of Thrombosis and Haemostasis, vol. 8, no. 9, September 2010, pp. 2063–2065. https://doi.org/10.1111/j.1538-7836.2010.03975.x.

5. Benlakhal, F. et al. “A retrospective analysis of 157 surgical procedures performed without replacement therapy in 83 unrelated factor vii-deficient patients.” Journal of Thrombosis and Haemostasis, vol. 9, no. 6, June 2011, pp. 1149–1156. https://doi.org/10.1111/j.1538-7836.2011.04291.x.

6. Chee, Y.L. et al. “Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures.” British Journal of Haematology, vol. 140, no. 5, March 2008, pp. 496–504. https://doi.org/10.1111/j.1365-2141.2007.06968.x.

7. Pfanner, G. et al. “Präoperative blutungsanamnese. empfehlungen der arbeitsgruppe perioperative gerinnung der österreichischen gesellschaft für anästhesiologie, reanimation und intensivmedizin.” Anaesthesist, vol. 56, no. 6, June 2007, pp. 604–611. https://doi.org/10.1007/s00101-007-1182-0.