Females who are carriers usually have enough clotting factors from their one normal gene to prevent serious bleeding problems, though some may present as mild haemophiliacs. Complications
Severe complications are much more common in cases of severe and moderate haemophilia. Complications may arise from the disease itself or from its treatment:
Deep internal bleeding, e.g. deep-muscle bleeding, leading to swelling, numbness or pain of a limb. Joint damage from haemarthrosis (haemophilic arthropathy), potentially with severe pain, disfigurement, and even destruction of the joint and development of debilitating arthritis. Transfusion transmitted infection from blood transfusions that are given as treatment. Adverse reactions to clotting factor treatment, including the development of an immune inhibitor which renders factor replacement less effective. Intracranial haemorrhage is a serious medical emergency caused by the buildup of pressure inside the skull. It can cause disorientation, nausea, loss of consciousness, brain damage, and death.Haemophilic arthropathy is characterized by chronic proliferative synovitis and cartilage destruction. If an intra-articular bleed is not drained early, it may cause apoptosis of chondrocytes and affect the synthesis of proteoglycans. The hypertrophied and fragile synovial lining while attempting to eliminate excessive blood may be more likely to easily rebleed, leading to a vicious cycle of hemarthrosis-synovitis-hemarthrosis. In addition, iron deposition in the synovium may induce an inflammatory response activating the immune system and stimulating angiogenesis, resulting in  cartilage and bone destruction. Genetics
Typically, females possess two X-chromosomes, and males have one X and one Y-chromosome.
Remitting seronegative symmetrical synovitis with pitting edema (or sometimes RS3PE) is a rare syndrome identified by symmetric polyarthritis, synovitis, acute pitting edema (swelling) of the back of the hands and/or feet, and a negative serum rheumatoid factor. If no underlying disorder can be identified (idiopathic RS3PE), this entity has an excellent prognosis and responds well to treatment.RS3PE typically involves the joints of the extremities, specifically the metacarpophalangeal and proximal interphalangeal joints, wrists, shoulders, elbows, knees and ankles. It is more common in older adults, with the mean age between 70 and 80 years in most studies. It occurs more often in men than in women with a 2:1 ratio. It is unknown how common this condition is. Signs and symptoms
Individuals affected by RS3PE typically have repeated episodes of inflammation of the lining of their synovial joints and swelling of the end portion of the limbs. The arms and hands are more commonly affected than the legs and feet. Both sides are usually involved though RS3PE can affect only one side in certain cases. Causes
RS3PE is a constellation of symptoms that can be caused by many other conditions. Since there is no definitive diagnostic test, other conditions have to be ruled out before this rare condition can be diagnosed. The main differential diagnosis is polymyalgia rheumatica (PMR), although pain, stiffness and weakness at the level of the shoulders and pelvic girdle with associated systemic symptoms (fever, malaise, fatigue, weight loss) is more typical of PMR.