This review summarizes current data on the pathomechanisms and new genetic findings of combined factor V and VIII deficiency (CF5F8D). Congenital haemorrhagic disorders characterized by deficiency of two clotting factors comprise an interesting group. Among dual coagulation disorders, CF5F8D is the most common type. For the first time combined factor V and VIII deficiency (F5F8D) was reported by Oeri et al in 1954. That is distinct from the coinheritance of both FV deficiency (parahaemophilia) and FVIII deficiency (haemophilia A) that has been reported in four families. Individuals who present with this phenotype have between 5 and 30% of normal plasma levels of FV and FVIII antigen and activity, whereas the level of other plasma proteins are not altered. Total numbers of affected individuals are less than 150 cases all over the world. At first it was assumed that deficiency of protein C inhibitor was a responsible cause, but further investigations revealed that it was due to mutations called ERGIC-53 and LMAN-1.

Presence of inhibitor to factor VIII (FVIII) is a rare occurrence. The incidence of acquired inhibitors in the population is 0.2-1 per million / year and majority of such patients are older than 60 years. Presence of these antibodies is observed sometimes in association with an autoimmune disorder, hematologic and nonhematologic malignancies, pregnancy, drug usage, infection and or idiopathy. Patients commonly present with hemorrhage into soft tissue ecchymosis, overt bleeding after trauma or surgery. Laboratory tests shows prolonged partial thromboplastin time (PTT), decreased level of factor VIII and increased level of factor VIII inhibitors. These patients are treated with prednisolone and cyclophosphamide. Hereby, we report a 75 years old man with ecchymosis and swelling of left knee, prolonged PTT, decreased FVIII level and increased FVIII inhibitor. He was treated with prednisolone and was followed up for any compliant or symptoms.He improved symptomatically within 15 days. After one month, he had no symptoms of disorder and normal PTT. However, after discontinuation of prednisolone, PTT level raised again and cyclophosphamide was prescribed. PTT was normal after one month.

Aptamers are oligonucleotide ligands of synthetic single-stranded DNA/RNAs (ssDNA/RNA) with specific conformations which were created by in-vitro selection from a large random sequence pool, based on the affinity between oligonucleotides and the specific target molecules. This screening method is called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Aptamers' unique characteristics in protein binding have made them highly valuable tools for different diagnostic applications, downstream purification processes, analysis, new drug development and drug delivery. One of the important and valuable therapeutic plasma proteins is human coagulation factor VIII (FVIII). In this investigation, FVIII was prepared from plasma source or recombinant production media and considered as a model protein for designing and development of relevant oligonucleotide aptamers. As the first step, random oligonucleotide library and its specific primers were designed and then chemically synthesized. After induction of 3D conformation by a specific temperature treatment, the random library was incubated with plasma derived FVIII. Gel filtration method was then employed as a partitioning step. During SELEX process, for the elimination of nonspecific cross interactions by other plasma proteins, two steps of negative selections were run. Finally, SELEX process was stopped when no more increase in the affinity constant (Kd) was observed and therefore the enriched pool was cloned. As the final step, protein affinity of enriched pools was determined using fluorescence method. It was found that the calculated Kd for enriched pools were 0.5 to 60nM and that they are comparable to the other specific ligands of the target protein.

Patients with coagulation factor(s) deficiency who use coagulation therapy are susceptible to forming inhibitors against coagulation factor(s). In this survey we detected factor V and VIII inhibitor in ten patients with combined deficiency of factors V and VIII from north east of Iran (Khorassan province). It was revealed in our survey that eight patients had both factor V and factor VIII inhibitors and two patients had none. Because factor V and factor VIII share approximately 40% amino acid sequence homology in their A and C domains, it remains to be elucidated if it is one molecule that recognizes both factor V and VIII or whether there are two inhibitor molecules against common sites.