Haemophilia part 2 (Diagnostic and therapy)

ANAMNESTIC

 Until now the family history is still the best way to do the first riddle of the cases of haemophilia, although there are 20-30% of cases of haemophilia, found X chromosome due to spontaneous mutation in the gene encoding F VIII / F IX. A boy - he allegedly suffered from haemophilia, if there is a history of recurrent bleeding (hemartrosis, hematoma) or a history of bleeding after trauma or stretching certain actions with or without family history.

Antenatal diagnosis can actually be done on pregnant women with risk. Examination of factor VIII activity and antigen levels of F VIII in the blood of the fetus in the second trimester fetus can determine the status of the vulnerability of haemophilia A. Identification of F VIII gene and the gene marker for better and more advisable.
A woman suspected of being the bearer of the nature of haemophilia (career) if he has more than one boy or haemophilia patients have one or more brothers and a young boy or his father's haemophilia patients with haemophilia patients. Detection of haemophilia A career can be done by calculating the ratio F VIIIc activity with antigen F VIIIvW. If the value is less than one has accuracy in determining the career of about 90% of haemophilia, but the heart - the heart on the state of pregnancy, hormonal contraceptive use and the presence of liver disease as it can increase the activity factor VIIIc. F VIII activity - average 50% on a career, but sometimes - sometimes <30% and bleeding can occur after trauma or surgery. Genetic analysis using DNA probes, namely by finding polymorphic loci on chromosome X will provide more precise information.
Laboratory
Laboratory abnormalities found in hemostasis testing in disorders, such as lengthening clotting time (CT) and activated partial thromboplastin time (aPTT), thromboplastin generation test abnormality, with the bleeding and the prothrombin (PT) within normal limits.
Definitive diagnosis established by reduced activity of factor VIII / factor IX, and if facilities are available can be performed cytogenetic examination examination seventh marker gene F / F IX. Activity of F VIII / F IX is expressed in U / ml with a mean activity of clotting factor in 1 ml of normal plasma was 100%. Normal value of F VIII activity / F IX was 0.5 to 1.5 U / ml or 50-150%. Must remember is to distinguish haemophilia A with Von Willebrand diseases, by looking at the ratio of F VIIIc: F VIIIag and activity F VW (ristosetin test) lower.

DIFFERENTIAL DIAGNOSTIC

• Haemophilia A and B with a deficiency of factor XI and XII
• Haemophilia A with Von Willebrand disease (especially the Normandy variant), acquired factor VIII inhibitor and a combination of factor VIII deficiency and factor V congenital.
• Haemophilia B with liver disease, the use of warfarin, vitamin K deficiency, F IX inhibitors is very rarely obtained.

SUPPORTIVE THERAPY

Rational treatment of haemophilia is to normalize the levels of factor antihaemophilia. But there are some things that must be considered
• Perform both avoid injury prevention / conflict
• Plan and maintain a surgical level of clotting factor activity approximately 30-50%
• To overcome the acute bleeding that occurs then the first action that rest, ice, compresio, elevation (RICE) at the location of bleeding
1. Corticosteroids. 

Very helpful to eliminate the acute inflammatory process in sinovitis hemartrosis which happened after the attack. Prednisone 0.5 to 1 mg / kg / day for 5-7 days can prevent the occurrence of residual symptoms such as stiff joints (artrosis) that interfere with daily activities and reduced quality of life for haemophilia patients
2. Analgesic.

Analgesic usage is indicated in patients with severe pain hemartrosis, and should be selected analgesic that does not interfere with platelet aggregation (to avoid usage of aspirin and anticoagulants)
3. Medical Rehabilitation. 

Should be performed as early as possible in a comprehensive and holistic in a team, because the delay would cause the management of both physical disability and disability, occupational and psychosocial and medical edukasi.Rehabilitasi arthritis, haemophilia include: training active / passive, cold and heat therapy (liver - liver), ortosis use, psychosocial therapy and therapeutic recreation also education. 

4. Replacement therapy Clotting Factor
Giving clotting factors are given three times a week to avoid a physical disability (especially joints) so that patients can do normal activities. But to achieve that goal is needed of factors antihemofilia (AHF) is quite a lot with the high cost. Clotting factor replacement therapy in cases hemofili done with F VIII or FIX, either recombinant, concentrates, or blood components that contain quite a lot of factors - such clotting factors. The provision made in a few days until the wounds or swelling improved, and particularly during physiotherapy.
Concentrated F VIII / F IX
Haemophilia A severe or mild and moderate to serious bleeding episodes requiring clotting factor correction with high levels should be treated with F VIII concentrate that has been attenuated virus. Factor IX is available in two forms namely prothrombin Complex Concentrates (PCC) which contains F II, VII, IX, X, and purified FIX Concentrates which contain a number of F IX without other factors. PCC can cause paradoxical thrombosis and coagulation due to intravenous spread by a number of other clotting factor concentrates. Risks can be increased in the provision of factor IX concentrate repeated so purified F IX is more desirable.

A. AHF Cryopresiptat
Is one of the non-cellular blood components that are specific plasma concentrates containing F VIII, fibrinogen, factor Vonwillebrand. May be granted if the F VIII concentrates is not found. One bag contains Cryopresiptat 80-100 UF VIII. One bag containing 100 UFCryopresiptat
B. One-deamino 8-D Arginine vasopressin (DDAVP) or desmopresin
Synthetic anti-diuretic hormone (DDAVP) to stimulate increased levels of F VIII activity in plasma up to four times, but it is temporary. Until now the mechanism of DDAVP is not known entirely, but was recommended to be given to mild and moderate haemophilia A and also on women's careers are symptomatic. Giving can be administered intravenously at a dose of 0.3 mg / kg bw in the 30-50 0.9% NaCl for 15-20 minutes with eight-hour work period. Effect on the granting of this peak reached in 30-60 min. In the year 1994 has been issued in the form of concentrates DDAVP intranasal spray. The recommended dose for patients with body weight <50 kg 150 mg (one spray), and 300 mg for patients with BW> 50 kg (twice a spray), with peak effects after 60-90 minutes. Giving DDAVP for the prevention of bleeding events should be performed every 12-24 hrs. Side effects that may occur in the form of tachycardia, flushing, thrombosis and hyponatremia. Angina can also occur in patients with coronary heart disease
C. Antifibrinolitik
Used on the B haemophilia patients to stabilize the clot / fibrin fibrinolysis by inhibiting the process. This proved very helpful in the management of haemophilia patient with bleeding, especially in cases of oral mucosal bleeding caused by the extraction of teeth because saliva contains an enzyme firinolitik. Epsilon Aminocaproic Acid (EACA) can be given orally or intravenously with an initial dose of 200 mg / kg, followed by 100 mg / kg body weight every six hours (maximum of five grams of each delivery). Tranexamic acid is given a dose of 25 mg / kg body weight (maximum 1.5 g) was administered orally or 10 mg / kg BW (maximum 1 g) intravenously every 8 hours. Tranexamic acid can also be reconstituted with 10% of parenteral fluids, especially the normal saline. 
D. Gene Therapy
The study of gene therapy using retrovirus vectors, adenovirus, and adeno - associated virus provides new hope for patients with haemophilia. Currently under intensive research by moving vivo adenovirus vector carrying the gene into liver cells antihaemophilia. F VIII gene are relatively more difficult than the F IX gene, because of its size (9kb) is bigger, but the end of 1998, the experts succeeded in moving the plasmid - based ex vivo factor VIII into the fibroblasts.
E. FFP (the Fresh Frozen Plasma)  clotting blood cell that has been taken from the red blood transfusion of FFP usually  Perform weight depending on whether haemophilia suffered. If patients with severe levels of the patients had to perform a transfusion of FFP 3x a week, but particularly if it was bleeding that resulted kebengkakan specific area then the transfusion should be done every day until the swelling has become lost. One bag containing the plasma, clotting factors, the complement , and plasma protein, the volume of a bag of FFP is 200-250 ml given six hours after the withdrawal, ABO match, 4-6 units could enhance coagulation factor 20-30%.

COMPLICATIONS
Arthropathy hemophilia: the accumulation of intra-articular blood who settled with the result of degeneration of cartilage and bone joints progressively. This causes a decrease until the destruction of joint function. Hemartrosis that are not managed properly can also cause sinovitis chronic synovial tissue inflammation due process is not endless. Joints that often develop complications are knee joints, ankles and elbows.
Prolonged bleeding due to medical action is often found if not done by providing preventive therapy for hemophilia blood clotting factor and weight are in accordance with the kind of medical practice itself (tooth extraction, circumcision, appendectomy, surgery thoracal / intra-abdominal). While bleeding due to trauma are common in everyday situations such as hemartrosis, intramuscular hemorrhage and hematoma. Intracranial hemorrhage is rare, but if  happened, it would be fatal