fkg minggu 2
TRANSCRIPT
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Bleeding Disorders
Indra Wijaya
Internal MedicineHasan Sadikin Hospital - Medical FacultyPadjadjaran University
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Objectives
Coagulation factor disorders and treatment
Disorders of platelets and platelettransfusion
Adjunctive drug therapy for bleeding
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Objectives
Coagulation factor disorders andtreatment
Disorders of platelets and platelettransfusion
Adjunctive drug therapy for bleeding
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Coagulation factor disorders
Inherited bleedingdisorders
Hemophilia A and B
vonWillebrands diseaseOther factor
deficiencies
e.g: Factor XI deficiency,etc
Acquired bleedingdisorders
Liver disease
Vitamin K deficiency/Warfarin overdose
DIC
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Hemofilia
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Hemophilia A and BHemophilia A Hemophilia B
Coagulation factor deficiency Factor VIII Factor IX
Inheritance X-linked X-linkedrecessive recessive
Incidence 1/10,000 males 1/50,000 males
Severity Related to factor level
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Hemophilia
Clinical manifestations (hemophilia A & B
indistinguishable)
Hemarthrosis (most common)
Fixed jointsSoft tissue hematomas (e.g., muscle)
Muscle atrophy
Shortened tendons
Other sites of bleeding
Urinary tract
CNS, neck (may be life-threatening)
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Factor VIII concentrate or Recombinant(Koate/Kogenate)
Dosage based on desired factor VIII increase (%):
Body weight (kg) x 0.5 int. units/kg x desired factor
VIII increase (%) = int. units factor VIII required
For example: 50 kg x 0.5 int. units/kg x 30 (% increase) =
750 int. units factor VIII
Dosage based on expected factor VIII increase (%):
(# int. units administered x 2%/int. units/kg) dividedby body weight (kg) = expected % factor VIII increase
For example: (1400 int. units x 2%/int. units/kg) divided by 70
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General Guidelines F VIIIconcentrate/recombinant
Minorhemorrhage: 10-20int. units/kg as a
single dose toachieve FVIII
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Treatment of hemophilia B
Agent
High purity factor IX
Recombinant human factor IX
DoseInitial dose: 100U/kg
Subsequent: 50 U/kg every 24 hours
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von Willebrand Disease
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von Willebrand Disease
von Willebrand factor: Carrier of factor VIIIAnchors platelets to subendothelium
Bridge between platelets
Inheritance Autosomal dominant (tipe 1 and 2)Autosomal recessive (tipe 3)
Incidence 1/10,000
Majority of these people do not have
symptoms
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von Willebrand Disease
present with varying degrees ofbleeding tendency, usually in the formof easy bruising, nosebleeds andbleeding gums. Women mayexperience heavy menstrual periodsand blood loss during childbirth.
http://en.wikipedia.org/wiki/Bleeding_tendencyhttp://en.wikipedia.org/wiki/Epistaxishttp://en.wikipedia.org/wiki/Menorrhagiahttp://en.wikipedia.org/wiki/Childbirthhttp://en.wikipedia.org/wiki/Childbirthhttp://en.wikipedia.org/wiki/Menorrhagiahttp://en.wikipedia.org/wiki/Epistaxishttp://en.wikipedia.org/wiki/Bleeding_tendency -
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Laboratory evaluation of von Willebranddisease
ClassificationType 1 Partial quantitative deficiency
Type 2 Qualitative deficiency
Type 3 Total quantitative deficiency
Diagnostic tests:von Willebrand type
Assay 1 2 3
vWF antigen
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Treatment of von Willebrand diseaseVaries by Classification
CryoprecipitateSource of fibrinogen, factor VIII and VWF
Only plasma fraction that consistently contains VWFmultimers
Correction of bleeding time is variable
DDAVP (Deamino-8-arginine vasopressin) Increases plasma VWF levels by stimulating secretion from
endothelium
Duration of response is variable
Used for type 1 disease
Dosage 0.3 g/kg q 12 hr IV
Factor VIII concentrate (Humate-P) Virally inactivated product
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Bleeding disorder of Sistemicdisease
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Liver Disease
Decreased synthesis ofII, VII, IX, X, XI, and fibrinogenProlongation of PT, aPTT and Thrombin Time
Treatment
Fresh-frozen plasma infusion (immediate but temporaryeffect)
Vitamin K (usually ineffective)
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Vitamin K deficiency
Source of vitamin K Green vegetablesSynthesized by intestinal flora
Required for synthesis Factors II, VII, IX ,XProtein C and S
Causes of deficiency MalnutritionBiliary obstruction
Malabsorption Antibiotic therapy
Treatment Vitamin KFresh frozen plasma
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Coagulation cascade
Vitamin K dependant factors
XIIa
IIa
Intrinsic system (surface contact)
XII
XI XIa
Tissue factor
IX IXa VIIa VII
VIII VIIIa
Extrinsic system (tissue damage)
X
V Va
II
Fibrinogen Fibrin
(Thrombin)IIa
Xa
Vit i K d fi i d t f i
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Vitamin K deficiency due to warfarinoverdoseManaging high INR values
Clinical situation Guidelines
INR therapeutic, < 5 Lower or omit next dose;Resume therapy when INR is therapeutic
INR 5-9; no bleeding Lower or omit next dose;Resume therapy when INR is therapeutic
Omit dose and give vitamin K (1-2.5mg po)
Rapid reversal: vitamin K 2-4 mg po (repeat)
INR >9; no bleeding Omit dose; vitamin K 3-5 mg po; repeat asnecessary
Resume therapy at lower dose when INR therapeuticChest 2001:119;22-38s(supplement)
Vit i K d fi i d t f i
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Vitamin K deficiency due to warfarinoverdoseManaging high INR values in bleeding patients
Clinical situation Guidelines
INR > 20; serious bleeding Omit warfarinAny life-threatening bleeding Vitamin K 10 mg slow IV infusion
FFP factor rhVIIa (depending on urgency)
Repeat vitamin K injections every 12 hrs as needed
Disseminated Intravascular Coagulation
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Disseminated Intravascular Coagulation(DIC)Mechanism
Depletion of plateletsand coagulation factors
Systemic activationof coagulation
Thrombosis of smalland midsize vessels
with organ failure
Bleeding
Intravasculardeposition of fibrin
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Common clinical conditionsassociated with DIC
Sepsis
Trauma
Head injury
Fat embolism
Malignancy
Obstetrical complications
Amniotic fluid embolism Abruptio placentae
Vascular disorders
Reaction to toxin (e.g. snakevenom, drugs)
Immunologic disorders Severe allergic reaction
Transplant rejection
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DICTreatment approaches
Treatment of underlying disorder
Anticoagulation with heparin
Platelet transfusion
Fresh frozen plasma
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Objectives
Coagulation factor disorders andtreatment
Disorders of platelets and platelettransfusion
Adjunctive drug therapy for bleeding
i f bl di i
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Sites of bleeding inthrombocytopeniaSkin and mucous membranes
PetechiaeEcchymosisHemorrhagic vesiclesGingival bleeding and epistaxis
MenorrhagiaGastrointestinal bleeding
Intracranial bleeding
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Petechiae
Do not blanch with pressure(> < angiomas)
Not palpable(> < vasculitis)
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Classification of platelet disorders
Quantitativedisorders
Abnormal distribution
Dilution effectDecreased production
Increased destruction
Qualitative disorders
Inherited disorders (rare)
Acquired disorders
MedicationsChronic renal failure
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Acquired thrombocytopenia withshortened platelet survival
Associated withbleeding
Immune-mediatedthrombocytopenia(ITP)
Most drug-inducedthrombocytopenias
Most others
Associated withthrombosis
Thromboticthrombocytopenic purpura
DIC
Heparin-associatedthrombocytopenia
h h h b i
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Approach to the thrombocytopenicpatient
History Is the patient bleeding?
Are there symptoms of a secondary illness? (neoplasm, infectionautoimmune disease)
Is there a history of medications, alcohol use, or recenttransfusion?
Are there risk factors for HIV infection? Is there a family history of thrombocytopenia?
Do the sites of bleeding suggest a platelet defect?
Assess the number and function of platelets
CBC with peripheral smear Platelet function study
Platelet transfusions -
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Platelet transfusions complicationsTransfusion reactions
Higher incidence than in RBC transfusions Related to length of storage
Bacterial contamination
Platelet transfusion refractoriness
Alloimmune destruction of platelets (HLA antigens)Non-immune refractoriness
Microangiopathic hemolytic anemiaCoagulopathySplenic sequestrationFever and infection
Medications (Amphotericin, vancomycin, ATG, Interferons)
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Kebutuhan transfusi trombosit
Penyebabtrombositopenia
Derajattrombositopenia
Penyakit Penyerta
Fungsi trombosit
Jenis operasi.Transfusi akan mampu bertahan empat hari
Transfusi trombosit konsentrat pada ITPsebaiknya dihindari
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Objectives
Coagulation factor disorders andtreatment
Disorders of platelets and platelettransfusion
Adjunctive drug therapy for bleeding
Adj ncti e dr g therap for
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Adjunctive drug therapy forbleeding
Fresh frozen plasma Cryoprecipitate Epsilon-amino-caproic acid (Amicar)
DDAVP Recombinant human factor VIIa(Novoseven)
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Fresh frozen plasma
Content - plasma (decreased factor V and VIII)
Indications
Multiple coagulation deficiencies (liver disease, trauma)
DIC
Warfarin reversal
Coagulation deficiency (factor XI or VII)
Dose (225 ml/unit) 10-15 ml/kg
Note Viral screened product
ABO compatible
Cryoprecipitate
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Cryoprecipitate
Prepared from FFP
ContentFactor VIII, von Willebrand factor, fibrinogen
IndicationsFibrinogen deficiency
Uremiavon Willebrand disease
Dose (1 unit = 1 bag)1-2 units/10 kg body weight
A i i id (A i )
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Aminocaproic acid (Amicar)
Mechanism
Prevent activation plaminogen -> plasmin
Dose 50mg/kg po or IV q 4 hr
Uses
Primary menorrhagia Oral bleeding
Bleeding in patients with thrombocytopenia
Blood loss during cardiac surgery
Side effects GI toxicity
Thrombi formation
D i (DDAVP)
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Desmopressin (DDAVP)
Mechanism
Increased release of VWF from endothelium
Dose 0.3g/kg IV q12 hrs
150mg intranasal q12hrs
Uses Most patients with von Willebrand disease
Mild hemophilia A
Side effects
Facial flushing and headache Water retention and hyponatremia
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Tranexamic acid (Kalnex)
MECHANISM OF ACTION Forms areversible complex that displacesplasminogen from fibrin resulting ininhibition of fibrinolysis; it also inhibits the
proteolytic activity of plasmin
Hemophilia patient:
during and following tooth extraction:I.V.: 10 mg/kg immediately before surgery,
then 25 mg/kg/dose orally 3-4 times/day for
Recombinant human factor VIIa
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Recombinant human factor VIIa(rhVIIa; Novoseven)
Mechanism
Activates coagulation system through extrinsicpathway
Approved UseFactor VIII inhibitors in hemophiliacs
Dose: (1.2 mg/vial)
90 g/kg q 2 hrAdjust as clinically indicated
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Summary
Identify and correct any specific defect ofhemostasis
Use non-transfusional drugs wheneverpossible
RBC or blood component transfusion forsurgical procedures or large blood loss