Recurrent miscarriage in a woman with congenital factor V deficiency: a case report.

BACKGROUND: Factor V deficiency is a rare bleeding disorder that can be either congenital or acquired. Factor V deficiency mostly present with mucosal bleeding. Coagulation factor V does not increase considerably during normal gestation. Since pregnancy can be threatened by blood clotting disorders, abnormal changes in coagulation factors level can pose challenges to pregnant women. CASE PRESENTATION: We report a 40-year-old pregnant woman with prolonged gingival bleeding and epistaxis at 28 weeks of pregnancy. Her past medical history included two unexplained abortions. Physical examination was unremarkable, but the blood test showed elevated PT and PTT with a considerable decrease in factor V activity, while other factors were within normal range. Subsequently, the patient was diagnosed with congenital factor V deficiency. After treatment with fresh frozen plasma, she underwent vaginal delivery and a baby with factor V deficiency was born. CONCLUSIONS: This is the second report of recurrent miscarriage in congenital factor V deficiency patients. Clinicians should consider the possibility of factor V deficiency in women with a history of idiopathic miscarriage even in patients without any symptoms.

Congenital coagulation factor V deficiency with intracranial hemorrhage.

BACKGROUND: Congenital coagulation factor V (FV) deficiency is a very rare hemorrhagic disease with an incidence of approximately one in a million. The common clinical manifestations of FV deficiency include ecchymosis and mucosal bleeding. Life-threatening intracranial bleeding is rare. It has been reported in several cases. However, the molecular basis has been established in only a few cases. METHODS: We reported a 2-month-old girl with congenital FV deficiency and intracranial hemorrhage. Coagulation screening combined with clinical manifestations was performed to diagnose congenital FV deficiency. Genetic testing was performed to identify the pathogenic genes. A literature review was included to emphasize the clinical manifestation, diagnosis, and treatment for congenital FV deficiency with intracranial bleeding. RESULTS: The coagulation tests revealed a significantly prolonged prothrombin time (PT) of 51 s and an activated partial thromboplastin time (APTT) of 73.7 s. The patient had a plasma FV activity of 0.9%. Genetic testing showed compound heterozygous mutations of the patient's FV gene. A literature review showed that patients with homozygous or compound heterozygous variants of the FV gene were often associated with a severe bleeding phenotype. CONCLUSION: Our study provides a direction for the rapid and accurate diagnosis and treatment for FV deficiency to avoid life-threatening bleeding. Infants with spontaneous cranial hematoma and intracranial hemorrhage should be investigated for underlying hemostatic defects. Congenital coagulation factor deficiency should be considered. Once congenital FV deficiency is diagnosed, fresh frozen plasma (FFP) should be given on a regular basis. Liver transplantation may be performed in severe cases.

[Clinical features of five cases of acquired factor V deficiency].

Acquired factor V deficiency is a rare disease that presents with various bleeding symptoms because of the acquired production of factor V inhibitors and decrease in factor V activity. We have experienced five cases of acquired factor V deficiency diagnosed on the basis of abnormalities in coagulation tests in the last 10 years. All five patients were older men, of whom one had no bleeding symptoms, and three had a history of renal failure and malignant tumors. In the cross-mixing test, two of three cases demonstrated an inhibitor pattern, but one case showed a deficient pattern. In all cases, steroid treatment improved factor V activity as well as prothrombin time and activated partial thromboplastin time. However, patients with intracranial hemorrhage had a poor prognosis. Although this disease is rare, careful management is necessary, especially in the absence of bleeding symptoms and where cross-mixing test does not show an inhibitor pattern.

Low factor V level ameliorates bleeding diathesis in patients with combined deficiency of factor V and factor VIII.

Combined factor V (FV) and FVIII deficiency (F5F8D) is a rare autosomal-recessive bleeding disorder caused by mutations in lectin mannose binding-1 (LMAN1) and multiple coagulation factor deficiency-2 (MCFD2). Six causative homozygous mutations (5 in LMAN1 and 1 in MCFD2) were identified in 6 patients with F5F8D. A thrombin-generation assay, triggered with tissue factor (1 pM) in F5F8D plasma, paradoxically exhibited enhanced thrombin generation compared with normal plasma. Significantly lower free tissue factor pathway inhibitor (fTFPI) was found in F5F8D patients compared with healthy controls (P < .01). Normalizing tissue factor pathway inhibitor α (TFPIα) in F5F8D plasma greatly delayed and reduced thrombin generation. Increasing FV concentrations by adding plasma FV to F5F8D plasma only caused a gradual decrease in thrombin generation, suggesting that low levels of TFPIα and FV cocontributed to the elevated thrombin generation by reducing anticoagulant effects. On the contrary, thrombin generation in F5F8D platelet-rich plasma (PRP) was significantly lower than in normal controls (P < .05); however, it was fully corrected by normalizing FVIII or after 1-deamino-8-d-arginine vasopressin (DDAVP) infusion, indicating that the hypocoagulable state of F5F8D patients is associated with low FVIII levels. In addition, plasma and platelet FV in F5F8D PRP were sufficient to support normal thrombin generation, and low TFPIα may have no effect on thrombin generation. DDAVP infusion induced a complete response in 5 F5F8D patients and a partial response in the remaining patient. Based on our findings, we suggest that DDAVP may be considered a potential substitute for FVIII concentrates, and fresh-frozen plasma (FFP) infusion may not be necessary for F5F8D patients with minor bleeding challenges.

Factor V activity in apheresis platelets: Implications for management of FV deficiency.

BACKGROUND: Allogeneic platelet (PLT) infusion is a strategy to raise Factor V (FV) levels in patients with congenital FV deficiency. However, since FV is labile in vitro, we hypothesized that FV activity could be low in PLT units. STUDY DESIGN AND METHODS: FV activity was tested using a prothrombin time-based platform in the supernatant and platelet lysate (PL) of apheresis PLT units (16 units stored in PLT additive solution with acetate and phosphate [PAS-C] and 10 units stored in plasma only), on post-collection days 3-6. Statistical analysis was performed using Student's t test (P < .05). RESULTS: FV activity was severely diminished in PAS-C PLTs (N = 16) supernatant (3.70% ± 1.02%) and PL (3.26% ± 1.02%). FV activity in plasma-only PLTs (N = 10) was lower in both supernatant (44.55% ± 6.46%) and lysate (39.67% ± 6.33%) relative to normal plasma levels, but both were significantly higher (P < .0001) compared to PAS-C PLTs. In a separate set of experiments, FV activity in PAS-C PLTs examined serially over storage time (N = 3 for these experiments) showed that FV levels were reduced by day 3 and not significantly different by day 5 of storage (Day 3 supernatant 5.03% ± 1.41%; Day 5 supernatant: 3.10% ± 0.57%; P = .2; Day 3 lysate: 3.89% ± 1.03%; Day 5 lysate: 2.61% ± 0.41%; P = .4). CONCLUSION: Plasma should be considered over PLTs as first-line therapy for non-complex FV deficiency-associated hemorrhage. If PLTs are considered for transfusion, plasma-only PLT units should be preferentially utilized, as PAS-C PLT have near-absent FV activity.

Plasma Exchange as an Initial Treatment for Severe Bleeding Induced by Acquired Factor V Deficiency: A Case Report and Mini Literature Review.

Acquired factor V deficiency (AFVD) is a rare autoimmune bleeding disorder. Unlike acquired hemophilia, bypass therapies with recombinant activated factor VII and activated prothrombin complex concentrates are ineffective for severe bleeding due to AFVD. Although several treatment strategies have been attempted, a standard of care for severe hemorrhage induced by AFVD is lacking. Herein, we report a case of AFVD with severe bleeding that responded to plasma exchange (PE) combined with immunosuppression. We also reviewed previously reported AFVD cases with severe hemorrhage and suggest that PE may be an effective initial treatment for AFVD-induced severe hemorrhage.

Platelet transfusion as treatment for factor V deficiency in the parturient: a case report.

BACKGROUND: Congenital factor V deficiency, also called parahemophilia, is a rare hematological disorder that can be treated with platelet transfusion. CASE PRESENTATION: A 27-year-old G2P0100 with factor V deficiency was admitted for induction of labor and requested labor epidural analgesia. Throughout her hospital course, factor V levels were managed per recommendation from her hematologist, which included transfusing fresh frozen plasma (FFP) to maintain a factor V level of 50% before any neuraxial technique and 40% for postpartum hemostasis. The parturient required multiple transfusions of FFP to stay at this level, which eventually resulted in pulmonary edema. Given the request to maintain high levels of factor V, the parturient was transfused with platelets as an alternative source of factor V. The parturient eventually delivered a healthy neonate without signs of postpartum hemorrhage or epidural hematoma. CONCLUSION: A major learning point from this case is that platelet transfusion is an effective alternative in the management of factor V deficiency. Factor V released by platelets has enhanced procoagulant function, resulting in local factor V concentrations 100 times more than that of plasma, and has a significantly extended half-life. Platelet transfusion should be considered as a therapy in treating parturients with factor V deficiency.

Management of intracranial hemorrhage in severe factor V deficiency and definitive treatment with liver transplantation.

FV is primarily produced in the liver, and congenital FV deficiency is a disorder with an incidence of one in 1 million. Standard care is to treat severe bleeding phenotypes with FFP as there is no recombinant or plasma-derived FV concentrate. We present a case of a neonate with known severe FV deficiency diagnosed after prolonged bleeding after circumcision who represented at age 2 months with a large left intraparenchymal hemorrhage. His bleed was treated with FFP, platelet transfusion, recombinant VIIa, and emergent evacuation. He was maintained on plasma infusions but was unable to space his infusions beyond 48 hours. Liver transplantation was considered as a definitive treatment for this condition. While awaiting a suitable liver, his FV trough levels occasionally dropped below 5%, and he suffered from a second acute intracranial bleed. He received an orthotopic liver transplant at age 5 months, resulting in correction of his FV levels. He has not required any plasma infusions post-transplantation and has had no further bleeding episodes. Liver transplantation should be considered as definitive treatment early in the course for patients with severe FV deficiency and first time life-threatening bleed.

Management of Single Uncomplicated Dental Extractions and Postoperative Bleeding Evaluation in Patients With Factor V Deficiency: A Local Antihemorrhagic Approach.

PURPOSE: The aim of the present study was to analyze the management of single dental extractions and postoperative bleeding in patients with a diagnosis of factor V deficiency. A careful evaluation of each case will allow the team to categorize the risk and operate safely, minimizing the incidence of intraoperative and postoperative complications. If necessary, the oral-maxillofacial surgeon can choose to do so in collaboration with the hematologist on a case-by-case basis. PATIENTS AND METHODS: The present retrospective study included 5 patients with mild congenital factor V deficiency who had undergone at least 1 dental extraction. Mouth rinse with tranexamic acid, nonresorbable sutures, and gelatin sponge packed in the alveolar socket were used to obtain hemostasis. No systemic therapies, such as fresh frozen plasma, platelet concentrate, or recombinant activated factor VII, were administered. RESULTS: Twenty-five teeth were extracted. The factor V plasma levels ranged from 14.1 to 22.4%. Local antihemorrhagic treatments resulted in good hemostasis. No hemorrhagic complications or intraoperative or postoperative major bleeding was observed. CONCLUSIONS: Dental extractions appear to be safe procedures for patients with mild factor V deficiency when a bleeding risk assessment has been performed in conjunction with a hematologist and an appropriate treatment protocol is followed. Our treatment protocol was found to be effective and well tolerated by all the patients.

Platelets and platelet-derived factor Va confer hemostatic competence in complete factor V deficiency.

Whole genome sequencing of an individual completely devoid of plasma- and platelet-derived factor V (FV) identified 167 variants in his F5 gene including previously identified and damaging missense mutations at rs6027 and Leu90Ser. Because the administration of fresh frozen plasma (FFP) prevents gastrointestinal bleeding in this individual, its effects on his plasma- and platelet-derived FV concentrations were assessed. The patient's plasma FV levels peaked by 2 hours following FFP administration and were undetectable 96 hours later. In contrast, increased platelet-derived FV/Va concentrations were observed within 6 hours, peaked at 24 hours, decreased slowly over 7 days, and originated from megakaryocyte endocytosis and intracellular processing of plasma FV. Ten days after transfusion, no thrombin was generated in a tissue factor-initiated whole blood clotting assay unless exogenous FV was added, consistent with the complete absence of plasma FV. In marked contrast, release of the patient's platelet-derived FV/Va (7% of normal) following platelet activation resulted in robust thrombin generation, similar to that in an individual with normal plasma- and platelet-derived FV concentrations. Thus, total FV deficiency can be corrected by plasma administration, which partially repletes and sustains the platelet cofactor pool, thereby highlighting the critical role of platelet-derived FV/Va in ensuring hemostatic competence.

Haemoperitoneum due to ruptured ovarian cyst in a 13-year-old girl with factor V deficiency- A case report.

Factor V deficiency is a rare autosomal recessive coagulation disorder. We are reporting a case of a 13 year old girl with factor V deficiency presenting as life threatening haemoperitoneum, following bleeding from ruptured ovarian cyst. Prolonged Prothrombin Time, Activated Partial Thromboplastin Time and a normal platelet count pointed towards a disorder of coagulation. Mixing study with factor V deficient plasma and coagulation factor assay revealed markedly reduced plasma factor V clotting activity.

Transfusion management of factor V deficiency: three case reports and review of the literature.

BACKGROUND: Factor V (FV) deficiency may be inherited as an autosomal recessive disease or acquired as a result of autoantibody formation, either spontaneously or secondary to exposure to bovine thrombin or medications. Congenital FV deficiency has traditionally been treated with plasma transfusions. However, recent evidence has suggested that platelet (PLT) transfusions may be a better alternative as FV stored within PLT alpha granules has greater procoagulant potential and is released locally at sites of vascular injury. We report three cases of FV deficiency, one congenital and two acquired, and emphasize the different management approaches. CASE REPORTS: Patient 1 was a 30-year-old man with congenital FV deficiency who presented with a trauma-induced hematoma of his lower extremity. He was treated with 5 PLT units over 48 hours. Patient 2 was a 64-year-old woman who presented with an upper-extremity thrombus and was discovered to have a FV inhibitor, likely secondary to antibiotics. Patient 3 was a 75-year-old woman with hepatitis C virus (HCV) who presented with minor ecchymosis and was found to have a FV inhibitor secondary to either HCV or antibiotic exposure. Corticosteroids alone were able to eradicate the inhibitors in both patients with acquired inhibitors. CONCLUSIONS: FV deficiency can present with a diverse range of symptoms. For bleeding patients, PLT transfusions should be the initial therapy. In patients with thrombosis, the risks and benefits of anticoagulation must be carefully assessed before treatment. For patients with minor bleeds, transfusions may be withheld, and elimination of the inhibitor should be the primary objective.

Acquired factor V inhibitor in a patient receiving venous-venous extracorporeal membrane oxygenation for Legionella pneumonia.

We report a rare complication of factor V deficiency in a patient having Legionella pneumonia. This patient also had other complications like severe acute respiratory distress syndrome, acute kidney injury, and septic shock that required venous-venous extracorporeal membrane oxygenation support. This is the first reported case of acquired factor V deficiency in a patient receiving extracorporeal membrane oxygenation for Legionella pneumonia. With the combined use of intravenous immunoglobulin, rituximab and plasma exchange, we achieved rapid clearance of the factor V inhibitor within 1 week so as to allow safe decannulation of extracorporeal membrane oxygenation.

The use of fresh frozen plasma for reproduction in severe factor V deficiency.

OBJECTIVE: Severe factor V (FV) deficiency is rare. There are case reports describing pregnancy outcomes in women with FV deficiency and one case report of successful pregnancy following the use of fresh frozen plasma (FFP) in several cycles of ovulation induction and intrauterine insemination and at delivery. The authors report another case to support the use of FFP for reproduction. CASE: A 27-year-old woman with severe FV deficiency was given FFP at the time of ovulation induced with clomiphene citrate, human menopausal gonadotropin (hMG), and human chorionic gonadotropin. Intrauterine insemination (IUI) was done 35 hours later. She became pregnant with twins and delivered vaginally at 36 weeks of gestation with the prophylactic use of FFP. CONCLUSION: Fresh frozen plasma can be offered for reproduction to women with severe FV deficiency.

Management of bleeding in severe factor V deficiency with a factor V inhibitor.

Factor V (FV) inhibitor arises rarely after using fresh frozen plasma (FFP) to treat inherited FV deficiency and is often a real therapeutic challenge. Here, we report a patient with a severe FV deficiency who developed such an inhibitor and was then treated with recombinant activated FVII (rFVIIa) and platelet concentrates (PC). Monitoring was assessed by thrombin generation assay (TGA). PC were more effective than rFVIIa in treating bleeding, but there was no correlation between the TGA results and clinical efficacy.

Severe postoperative hemorrhage caused by antibody-mediated coagulation factor deficiencies: report of two cases.

Antibody-mediated coagulation factor deficiencies constitute a rare disorder that may develop in elderly patients without any history of a bleeding diathesis. Patients may present with severe and sometimes catastrophic bleeding. We report two cases of postoperative hemorrhage caused by a coagulation factor deficiency. In Case 1, massive intraabdominal bleeding occurred on day 3 after pancreaticoduodenectomy for bile duct cancer, and was caused by an acquired inhibitor of coagulation factor VIII. Hemostasis was achieved and the factor VIII inhibitor titer decreased to zero with activated prothrombin complex concentrates, prednisolone, and cyclophosphamide. In Case 2, intraabdominal bleeding occurred on day 7 after hepatectomy for hepatocellular carcinoma, and was caused by an acquired inhibitor against factors II (prothrombin) and V. This patient was treated with hemostatic agents containing bovine thrombin during surgery and also with prednisolone. We report these cases to highlight that antibody-mediated coagulation factor deficiencies should be considered when an elderly patient suffers sudden postoperative hemorrhage and to stress the importance of prompt diagnosis because of the risk of potentially life-threatening hemorrhage.