Combined deficiency of factors V and VIII is a rare autosomal recessive disorder associated with an increased risk of bleeding. We present an unusual case of a 7-year-old Moroccan child with no history of consanguinity who was hospitalized owing to a hemorrhagic episode during circumcision. The 7-year-old patient, a Moroccan boy from North Africa, coming from a family of five siblings, was referred for an evaluation of prolonged activated partial thromboplastin time and prothrombin time. Coagulation factor assays revealed a combined deficiency of factors V and VIII, with normal levels of other coagulation factors. This anomaly was detected in the hematology laboratory, where hemostasis tests were performed via optical methods on the Acl Top 750 analyzer. A complete blood count was conducted on the Beckman Coulter DXH 900 analyzer. Hemostasis assessments revealed an elevated activated partial thromboplastin time at 73.2 s (normal range < 36), with a patient-to-control activated partial thromboplastin time ratio of 2.58 (normal ratio < 1.2), a low prothrombin time at 18.35 s (normal prothrombin time range: 11.4-13.5), and an international normalized ratio of 1.59 (normal range: 2-3.5). Specific coagulation factor assays demonstrated a combined deficiency of factors V and VIII at 12.4% (normal range: 55-150) and 9.1% (normal range: 50-145), respectively, whereas other coagulation factor levels remained within the normal range, including the antigenic activity of von Willebrand at 71.7% (normal range: 50-150). The complete blood count showed no abnormalities, except for a small thrombocytosis. The child was managed in the pediatric hematology department, and a family investigation among the remaining siblings was initiated to search for similar cases. Our study highlights a rare and often underdiagnosed genetic disorder that is often confused with a diagnosis of minor hemophilia A or congenital factor V deficiency. Differential diagnosis is crucial, particularly for von Willebrand disease. Combined deficiency of factors V and VIII should be suspected in patients with a suggestive clinical and laboratory profile, including prolonged prothrombin time and activated partial thromboplastin time along with a deficiency in coagulation factor V. Therefore, measuring factor VIII levels is highly recommended.

Combined deficiency of clotting factor V and factor VIII (DF5F8) is a congenital autosomal recessive disorder. This study involved a family of four children born to consanguineous parents. The eldest daughter was referred for assessment of activated partial thromboplastin time and prothrombin time associated with hemorrhagic manifestations. Coagulation factor dosing showed combined deficiency of factor V and factor VIII as well as normal levels of other coagulation factors. DF5F8 was detected in two girls and a boy. Two protein coding genes LMAN1 (lectin, mannose binding 1) and MCFD2 (multiple coagulation factor deficiency2) were involved in the intracellular passage of Factor V and Factor VIII, including some mutations which caused deficiency of Factor V and VIII. The diagnosis of DF5F8 is routinely possible, especially in patients born to consanguineous parents with a suggestive clinico-biological condition. Le déficit combiné en facteurs V et VIII de la coagulation (DF5F8) est un désordre constitutionnel de transmission autosomique récessif. C´est une famille de quatre enfants, issus de consanguinité. La fille aînée adressée pour exploration d´allongement du Temps de Céphaline avec activateur et du Temps de Quick, associé à des manifestations hémorragiques. Le dosage des facteurs de coagulation montre un déficit combiné en facteurs V et VIII, et taux normaux des autres facteurs de coagulation. On trouve un DF5F8 chez deux filles et un garçon. Deux gènes codent pour protéines LMAN1 (Lectin MANnose-Binding1) et MCFD2 (Multiple Coagulation factor deficiency2), sont impliquées dans le passage intracellulaire des FV et VIII, dont certaines mutations provoquent un déficit combiné en facteur V et VIII. Diagnostic du DF5F8 est possible en routine surtout chez des patients issus de consanguinité avec un contexte clinico-biologique évocateur.

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.

: Combined factor V and factor VIII deficiency is an extremely rare bleeding disorder for which research is lacking. We present the case of a 33-year-old man requiring repeat mitral valve replacement. A multidisciplinary team approach was utilized to minimize his risk of bleeding which included the use of plasma exchange, intravenous factor replacement, and platelet transfusion. This approach created an operative experience that did not require blood transfusion or the use of other hemostatic medications.