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![Treatment: The Old Days
Factor replacement
Units = (wt[kg]) x (50mL plasma/kg) x (1 U factor/mL plasma) x
(desired factor level – native factor level)
FFP: 10-20 mL/kg BB will increase factor level 20-30%
Number of unit : desire dose (mL)/200 mL/unit
Plasma concentrates
Thousands of donors
Hepatitis B, C
HIV (60-70%)](https://image.slidesharecdn.com/hemophilia-130127161535-phpapp01/85/Hemophilia-32-320.jpg)
Uploaded byTheo A.Y. Lemuel
Hemophilia
Hemophilia A and B are X-linked bleeding disorders caused by deficiencies of coagulation factors VIII and IX respectively. Hemophilia A is more common, affecting about 1 in 5,000-10,000 live male births. The disorders are inherited but only affect males, with female carriers able to pass the gene to their sons or daughters. Common clinical manifestations include hemarthrosis, hematomas, and intracranial bleeding. Treatment involves replacement of the missing coagulation factor, initially through plasma-derived or recombinant products, with the goal of preventing bleeds or treating acute bleeds.
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Hemophilia
- 1. Hemophilia A, B VonWillebrand disease disease Theo Audi Yanto
- 2.
- 3. Definition • Hemophilia- “loveof bleeding” • 2 types: A and B • Hemophilia A: • X linked recessive hereditary disorder that is due to defective or deficient factor VIII
- 4. Incidence • It isthe second most common inherited clotting factor abnormality (after von Willebrand disease) • 1 in 5000-10000 live male births • No difference between racial groups
- 6. Genetics • Transmitted by females, suffered by males • The female carrier transmits the disorder to half their sons and the carrier state to half her dtrs • The affected male does not transmit the disease to his sons (Y is nl) but all his dtrs are all carriers (transmission of defected X)
- 7. Russian House British House Spanish House
- 8. Hemophilia A FactorVIII deficiency 1 in 5000-10000 males 60% with severe disease Actvitiy < 1%
- 9. Hemophilia B FactorIX deficiency 1 in 25000-35000 males 30% spontaneous mutation 50% with mild to moderate disease Activity > 1% Christmas disease (1952)
- 13. •Deficiency of factorVIII or IX affects the propagation phase of coagulation •Most likely to cause bleeding in situations where tissue factor exposure is relatively low
- 14. Bleeds in Hemophilia •Minor Bleeds – Oral mucosa – Intra-articular – GI/GU – Intramuscular • Major Bleeds
- 15. ACUTE COMPLICATIONS OFHEMOPHILIA Hemarthrosis Muscle hematoma (pseudotumor) (joint bleeding)
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- 17. Clinical Manifestations: • Hemarthrosis The most common, painful and most physically, economically and psychologically debilitating manifestation. • Clinically: Aura: tingling warm sensation Excruciating pain Generally affects one joint at the time Most commonly: knee; but there are others as elbows, wrists and ankles. Edema, erythema, warmth and LOM If treated early it can subside in 6 to 8 hs and disappear in 12 to 24 hs. Ddx: DJD Complications: Chronic involvement with joint deformity complicated by muscle atrophy and soft
- 18. Nerve destruction Joint damage LONG-TERM COMPLICATIONS OF HEMOPHILIA
- 19. Clinical Manifestations Hemarthrosis-Images • Stage III- early Stage IV- narrowing of intraarticular space subchondral cyst
- 20. Clinical Manifestations Hematomas • Subcutaneous and muscular hematomas spread within fascial spaces, dissecting deeper structures • Subcutaneous bleeding spreads in characteristic manner- in the site of origin the tissue is indurated purplish black and when it extends the origin starts to fade • May compress vital structures: such as the airway if it is bleeding into the tongue throat or neck; it can compromise arteries causing gangrene and ischemic contractures are common sequelae, especially of calves and forearms • Muscle hematomas: 1)calf,2)thigh,3)buttocks,4)forearms • Psoas hematoma- if right sided may mimic acute appendicitis • Retroperitoneal hematoma: can dissect through the diaphragm into the chest compromising the airway. It can also compromise the renal function if it compresses the ureter
- 21. Clinical manifestations Pseudotumors • Dangerous and rare complication • Blood filled cysts that are gradually expanding • Occur in soft tissues or bones. • Most commonly in the thigh A pseudotumor is deforming the cortex of the femur (arrow). • As they increase in size they Other ossified masses in the soft tissues (arrowheads) are probably soft-tissue pseudotumors. erode contiguous structures. • May require radical surgeries or amputation, and surgery is often complicated with infection
- 22. Clinical manifestations Intracranial hemorrhage • Leading cause of death of hemophiliacs • Spontaneous or following trauma • May be subdural, epidural or intracerebral • Suspect always in hemophilic patient that presents with unusual headache • If suspected- FIRST TREAT, then pursue diagnostic workup • LP only when fVIII has been replaced to more than 50%
- 23. Clinical manifestations Severity F VIII activity Clinical manifestations Spontaneous hemorrhage from early infancy Severe <1% Freq sp hemarthrosis Hemorrhage sec to trauma or surgery Moderate 2-5% Occ sp hemarthrosis Hemorrhage sec to trauma or surgery Mild >5% Rare sp bleeding • Frequency and severity of bleeding are related to F VIII levels Coinheritance of prothrombotic mutations (i.e. Factor V Leiden) can decrease the risk of bleeding
- 24. History taking • signof Hemorrhage • Family history • infection related transfusion: • HIV, hepatitis realated symptom
- 25. Physical examination • Signof bleeding • Vital sign: tachycardia, tachypnea, hypotension, orthostasis • Organ system-specific sign of hemorrhage: • MSK, CNS, GI, GUT
- 26. Hemophilia: Work-up Hgb/Hct nml/low PT nml aPTT high/nml Platelets nml Factor levels (50-150%) Mild > 5% Moderate 1-5% Severe < 1% Inhibitor levels Low titer 0-10 Bethesda U High titer > 10 Bethesda U
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- 29. Normal PT Abnormal PTT 50:50 mix is Repeat abnormal with Test for inhibitor activity: 50:50 Specific factors: VIII,IX, XI mix Non-specific (anti-phospholipid Ab) 50:50 mix is normal Test for factor deficiency: Isolated deficiency in intrinsic pathway (factors VIII, IX, XI) Multiple factor deficiencies (rare)
- 30.
- 31. •Give factor q12 hours for 2-3 days after major surgery, continue with daily infusions for 7-10 days •Trough factor levels with q 12 h dosing after major surgery should be at least 50-75% •Most joint and muscle bleeds can be treated with “minor” (50%) doses for 1-3 days without monitoring
- 32. Treatment: The OldDays Factor replacement Units = (wt[kg]) x (50mL plasma/kg) x (1 U factor/mL plasma) x (desired factor level – native factor level) FFP: 10-20 mL/kg BB will increase factor level 20-30% Number of unit : desire dose (mL)/200 mL/unit Plasma concentrates Thousands of donors Hepatitis B, C HIV (60-70%)
- 33. Cryoprecipitate AHF (Antihemophilic Factor) (AntihemophilicFactor) Berisi Faktor VIII Faktor XIII Von Willebrand Factor dan fibrinogen (suhu simpan ≤30°C) Kandungan: 70 IU/unit F VIII dan > 140mg/unit fibrinogen 33
- 34. Replacement Therapy Plasma-derived Recombinent Heating 1990s Solvent- Cost detergent 2-3 x mixture Persistent inhibitors Hep A 10-15% Parvovirus B19 CJD
- 35. Factor VIII containing products Factor VIII, human plasma derived : Monarc M, Monoclonat, hemofil M, Koate-DVI, recombinate, kogenate, helixate, advate, xyntha 35
- 36. Factor VIII concentratesdiffer in purity and manufacturing processes Plasma-derived Recombinant Intermediate High Ultrapure Standard Human albumin- free Humate-P Koate-HP Hemofil-M Recombinate Advate Alphanate Monoclate Kogenate ReFacto-AF Monarc-M Helixate ReFacto
- 37. A little aboutcost Product Cost/dose Recombinant FVIII $4400 Monoclonal FVIII $3300 BeneFIX $8800 Mononine $8300 FEIBA $5000 NovoSeven $6500 x 2
- 38. Other meds •Amicar(epsilon aminocaproic acid) (antifibrinolytic) •DDAVP (antihemophilic)
- 39. Von Willebrand Disease • Inherited • Deficiency or dysfunction of vWF • vWF, a large, multimeric glycoprotein • mediate adhesion of platelet • bind and stabilized procoagulant FVIII
- 40. vWF • 125/1.000.000 •severe disease only 0.5-5/million • Male and female equaly • mild and manageable bleeding
- 41. vWD • 1) partialquantitative deficiency (type I) • (2) qualitative deficiency (type II) • (3) total deficiency (type III)
- 42. Work Up • Bleedingtime • PT and aPTT • vWD Factor Antigen • Ristocetin activity • vWD multimeric Panel • Genetic Testing
- 43. Presentation • Easily bruising •prolonged bleeding • severe hemorrhage after surgery • menorrhagia • Physical finding: usually normal, only sign of bleeding or bruises
- 44. Treament • Desmopressin DDAVP • 150 mcg intra nasal 2 h prior to procedure • Transfusion: Cryoprecipitate • Plasma derived: Humate-P (intermediate)
- 45. Disorder BT Plt PT aPTT TT Fib Vasculopathie s, connective tissue Normal or diseases, or Long Normal Normal Normal Normal increased* collagen disorders affecting skin Thrombocyto Long Low Normal Normal Normal Normal penia Qualitative Normal or platelet Long Normal Normal Normal Normal low• abnormalities Hemophilia A (factor VIII Normal Normal Normal Long Normal Normal deficiency) von Willebrand Long Normal** Normal LongΔ Normal Normal disease Disseminated intravascular Long Low Long Long Long Low coagulation