Prothrombin (Factor II) Deficiency

Differential Diagnosis

Given the wide range of bleeding symptoms reported in prothrombin deficiency, a broad differential diagnoses is possible, including the following conditions:

Hemophilia A
Hemophilia B
von Willebrand disease
Platelet function defects
Other rare factor deficiencies.

Conditions that should be differentiated from prothrombin deficiency are hemorrhagic disease of the newborn (HDN), liver disease, and vitamin K-dependent clotting factors deficiency (VKCFD). In all of these cases, all vitamin K-dependent coagulation factors are significantly decreased, including FII, FVII, FIX, FX, protein C, and protein S.

While HDN and liver disease are considered acquired conditions, VKCFD is a rare inherited coagulation disorder that arises from a single genetic defect of either the vitamin K 2,3-epoxide reductase complex or γ-glutamyl carboxylase. These enzymes are critically involved in vitamin K metabolism and post-translational modification of prothrombin.³²^,33 A defective enzyme results in combined deficiencies of FII, FVII, FIX, and FX. The genetic defect is inherited as an autosomal recessive trait and occurs in the absence of liver disease or malabsorption. Patients carrying the defective gene usually present early in life with intracranial or umbilical cord bleeding.

Another rare condition that can present with similar laboratory findings as prothrombin deficiency and a propensity for severe bleeding is lupus anticoagulant-hypoprothrombinemia syndrome (LAHS). LAHS is an acquired disorder that is characterized by bleeding or significant bruising, prolonged prothrombin time (PT) and activated partial thromboplastin time (PTT), and lupus anticoagulant with anti-prothrombin antibodies, resulting in acquired prothrombin deficiency.³⁴ LAHS predominantly affects children <16 years old and females. LAHS can be associated with an underlying autoimmune disorder; however, in children LAHS is typically a self-limited process that often occurs following a viral illness.³⁵