(14) hemorrhagic disease

8/10/2019 (14) Hemorrhagic Disease

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HAEMORRHAGIC

DISEASE


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Suspected of hemorrhagic disease :

1. Spontaneous bleeding

2. Prolonged bleeding/massive

3. More than one site bleeding

PATHOGENESIS

Hemostasis process :

- maintaining blood in a state of dilution

- maintaining blood in vascular- to stop bleeding vascular damage


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3 components of hemostasis:

HEMOSTASIS

THROMBOCYTE

Disturbance one of components homeostasisbleeding


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DETECTION OF HAEMORRAGIC DISEASE

Step I - good history taking- physical examination

- Trauma: - History of trauma chronologically- Mildtrauma bleeding- Severe spontaneous bleeding

- Quantity and duration of bleeding- Recurrent bleeding


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- trauma

always bleeding

Congenital hemorrhagic disease

- Deep tissue bleeding

( large hematom or hemarthrosis)Congenital hemorrhagic disease

- Petechie not congenital hemorrhagic disease

- Congenital hemorrhagic disease usually

coagulation disorder


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Laboratory examination :- Screening examination

- Specific examination

Screening examination :1. Platelet count

2. Bleeding time ( thrombocyte function)3. Prothombine time (PT)4. Activated partial tromboplastin time (APTT)5. Clotting observation / clotting retraction

Specific examination :

1. Coagulation factor (factor assay)2. Thrombocyte function :

aggregation, release reaction etc.


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VASCULAR DISORDER

Mostly : secondary vascular pupura :- Immunology: Schenlein-Henoch syndrome

- Infection: Virus, Rickets, Bacteria

- Drugs- Deficiency of Vit. C

- Uremia

Congenital:

- Hereditary hemorrhagic telangiectasia(Osler-Weber-Rendu)

- Cutishyperelastica (Ehler-danlos)


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Laboratory:

- platelet count normal

- bleeding time normal

- PT & APTTnormal

Clinical :- usually petechiae

skin & mucosaspontaneous

- Tourniquet test positive

- symptoms & signs of primary disease


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SCHENLEIN-HENOCH SYNDROME

Incidence :- 3 -7 years of age- Male : female = 3 : 2

Etiology:

Immunologic Reaction:

- Infection: beta hemolytic Streptococcal, Viral

- Food : milk, egg, tomato, fish etc.

- Drug : erythromycin, sulfa, penicillin, ect.

- Insect bite

- Allergic Purpura

- Anaphylactic Purpura


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CLINICAL MANIFESTATION

1. Skin involvement:

- erytema, maculopapuler- petechie & echymosis

Distribution of lesion: symmetric:

- extensor lower extremity- gluteus, hip- extensor arm elbow

2.Articular involvement:

- 75% case

- polyarthralgia/polyarthritis non-migrants- periarthriculer swelling- especiallyknee & ankle- full recovery


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4. Kidney involvement:

- 25-50% case 2-3 weeks

- proteinuria & hematuria (micro/macroscopic)

- often in male

- 5 -10% chronic

3. Stomach involvement:

Colic (50%) with : vomiting, diarrhea, melena

- mild to severe

umbilicus

- cause : edema & bleeding intestinal mucosa


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MANAGEMENT

self limiting symptomatic treatment

- Corticosteroid:

- intestinal mucosa edema

colic & invagination- arthricular involvement

- Bed restavoid intracranial bleeding


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-Good if no complication-Full recovery in 4 weeks

- Residive- Complication rare:

- invagination, intestinal perforation- intracranial bleeding- renal failure

PROGNOSTIC


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THROMBOCYTE DISORDER

A. QUANTITATIVE DISORDER

1. Thrombocytopenia bleeding

2. Thrombocytosis

thrombus formation

Normal:

platelet count 150.000 - 400.000/mm3

< 50.000/mm3spontaneous bleeding


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a. Production disorder:- Hypoproliferation: aplastic anemia, ATP

- Ineffectivethrombopoesis :

- Megaloblastic anemia

- ANLL M7

b. Distribution disturbance:

- Splenomegali: pooling thrombocyte

- Lymphoma

c. Dilution:

- Massive blood transfusion

THROMBOCYTOPENIA:


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d. Abnormal destruction- Non-immune: - DIC

- Infection: DHF, sepsis

- Immune:

- Idiopathic Thrombocytopenic Purpura (ITP)

- Drugs: Kina, kinidin, sulfa, dilantin, ect.

- Neonatal thrombocytopenia

- Purpura post-transfusion

e. Abnormal consumption:

- DIC, DHF


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1. Adhesion disturbance

2. Aggregation anomaly

Diphenydramin:

- prevent platelet aggregation

3. Disturbance of platelet release reaction

Asetil salisilic ac.:

- distrub release of ADP

- asetilasi platelet membrane

B. QUALITATIVE DISORDER= Trombastenia or thrombopati


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IDIOPATHIC/IMMUNETHROMBOCYTOPENIC PURPURA (ITP)

Destruction of platelet shorter ageimmunologic mechanism:

- antibody (IgG) platelet

- C3complement

- cellular immunity activation:

macrophage & cytotoxic cell


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CLASSIFICATION

1. Acute ITP (85-90%): self limiting children

2. Chronic ITP (10-15%): adult

- Age : 2 - 8 years

- 50% of cases : 1 - 6 weeks before

viral infection: ARTI, hepatitis, mumps,mononucleosus infectiosa,cytomegaloviral etc.)

ACUTE ITP


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- hemorrhagic skin & mucous membrane

petechie & ecchimosis

melena, hematury

- hemorrhagic of inner organ rare

- severely thrombocytopeni cerebral bleeding

- tourniquet test is positive

Clinic symptoms:


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- thrombocytopeni

- blood smear:

abnormal platelet form,

big size, separately

- decreaseof clot retraction

- prolonged ofbleeding time

- PT & APTT normal

Blood picture:


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Important exclude:- aplasticanemia

- leukemia

Megakaryocyte:

- Normal in quantity or increase- Morphology:

- immature- cytoplasm: more basophile- less granulation

Bone marrow:


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-Rest & avoid trauma

- Mild case doesn't need therapy

- Severely case massive hemorrhagic:

- corticosteroid- platelet suspension not suggested

- blood transfusion (PRC): on indication

Acute ITP therapy

- Mostly (85 - 90 %) recover

- 10 - 15%

chronic

Prognose:


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Chronic ITP

- Thrombocytopeni (< 100.000/mm3)

6 months- Spontaneous remission is very rare

- Age > 10 years, female > male

Therapy:

1. Corticosteroid

2. Immunosuppressive

if 1 failed3. IgG or Danazol

3. Sphlenectomy if 1, 2 & 3 failed


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COAGULATION

DISORDER

Coagulation component:

1. Blood Coagulation System

blood coagulation mechanism2. Anticoagulation System

prevent intravascular coagulation

maintain blood fluidity

3. Fibrinolytic System

fibrinolysis keep open the lumen of

blood vessels


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BLOOD COAGULATION SYSTEM

International Name Synonym

I Fibrinogen

II ProthrombinIII Tissue factor,

Tissue thromboplastin

IV Calcium (Ca)

V Proacelerin, Labile Factor

VII Proconvertin, Stable factor

VIII Antihemophilic Factor, AHF-A

Blood Coagulation Factors :


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IX Plasma Thromboplastin Component(PTC), Christmas Factor, AHF-B

X Stuart Prower Factor

XI Plasma Thromboplastin Antecedent(PTA), AHF-C

XII Hageman Factor, AHF-D

XIII Fibrin Stabilizing factor (FSF)

Prekalikrein Fletcher Factor

Kininogen Fitzgerald factor

BLOOD COAGULATION SYSTEM


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Coagulation Inhibitor:

- Antithrombin III

- C Protein & S Protein

- Alpha-2 macroglobulin

Plasminogen system- plasmin:- Plasminogen- Plasminogen activator- Anti plasmin

ANTICOAGULATION SYSTEM :

FIBRINOLYTIC SYSTEM :


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1.Prothrombin activator formation(Protrombinase):- Intrinsic- Ekstrinsic

2. Prothrombin trombin

3. Fibrinogen fibrin

Blood coagulation process :

Surface Contact Tissue damage


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Surface Contact

XII XIIa

XI XIa

IX IXa

X Xa X

III+

VII

V

F.Tr-3

Prothrombin Thrombin

Fibrinogen Fibrin

Fibrin polymer

XIII

PROTHROMBINASE

VIII

Ca++ Ca++

Ca++

Tissue damage

IN

TRINSIC

ExTRINSIC


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1. Coagulation System

2. Anticoagulation system

3. Fibrinolytic system

COAGULATION DISORDER

Disorder of coagulation system/mechanismone or more deficiency :

coagulation factor


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1. Decreased of synthesis :

- Genetic/congenital : Hemophilia

- Vit. K deficiencyII, VII, IX & X, C Protein

- Severe liver disease

2. Increase of demand

- Consumption coagulopathy

Disseminated Intravascular Coagulation(DIC)

l i i d h i i


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1. Bleeding mild injury, rarely spontaneously

2. Rarely petechie3. Bleeding joint & deep tissue

large hematoma, large ecchymoses4. Bleeding from wound :

- not immediately occur- often recurrent- prolonged (> 48 hours)- oozing

Laboratory:- PT & PTT: one or both increase

- Normal bleeding time

- Coagulation observation: fragile

Coagulation Disorder Characteristics :


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HEMOPHILIA


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INCIDENCE

1 : 10.000

Hemophilia A most common

GENETICS AND PATHOPHYSIOLOGY

- Factor VIII Gen X chromosome

- Gen mutation (substitution & deletion)

defects in factor VIII synthesis

Inherited recessively in connection withsex chromosomes : X-linked


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Male (XhY) affected

female (XhX)

carrier

Usually by marriage:

Normal father (X Y)

Carrier mother (XhX)

Hemophilia almost entirely in boys

GENETICS AND PATHOPHYSIOLOGY


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F VIII: protein plasma are needed inprothrombin activator synthesis process

Women could be affected:

- father = (XhY) & mother = (XhX)- Inactive gene of VIII factor

- Spontaneous mutation gene of VIII factor

F VIII deficiency

coagulation cascadedisturbance

GENETICS AND PATOPHYSIOLOGY


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CLINICAL MANIFESTATION:

Severe Hemophilia : F VIII < 1%

spontaneous bleeding

hemarthrosis, muscle bleeding,

gastrointestinal, hematuria & brain

Depends on F VIII levels

Moderate Hemophilia : F VIII 15 %bleeding after minor trauma

Mild Hemophilia : F VIII 625 %bleeding after major trauma,

surgery


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DIAGNOSIS

History:

- History of repeated bleeding

joints- Brothers with the same illness

- Brothers from mother with the same illness

Physical examination:- hemarthrosis, hematoma, etc

Laboratory:-normal platelet & bleeding time

- Prolonged PTT & normal PT

- TGT & AHF assay F VIII deficiency

COMPLICATION


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COMPLICATION

hemophilia arthropathycontracture and paresis/paralysis

of muscle

hemophilic pseudotumor

Formation antibody against F VIII

thrombosis

ITP

Viral hepatitis

Because of the disease:

Because of treatment:


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TREATMENT


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3. Bleeding prevention:

- prevention of trauma

- addition of F VIII before surgery

- contraindication: aspirin

TREATMENT

VITAMIN K DEFICIENCY


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VITAMIN K DEFICIENCY

Is found in:

1. Hemorrhagic disease of the newborn (HDN)

2. Disorder of Vit. K absorption:

- Biliary tract obstruction

- Chronic diarrhea

- Severe liver disease3. Intestinal sterilization by antibiotics

HEMORRHAGIC DISEASE OF THE NEWBORN


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HEMORRHAGIC DISEASE OF THE NEWBORN(HDN)

Hemorrhagic disease in newborn baby due to:

Deficiencies of factor II, VII, IX & X

vitamin K

Physiology (normal):

Coagulation factor II,VII,IX & X:

- decrease in newborn

the lowest rate at 2 - 5 days of age

- increase at 714 days of age

Etiology:

- Uncomplete colonization of intestinal flora

the synthesis of vit K in gut is still low

- decrease of vit K in placenta


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If decreasing of coagulation factor excessiveHDN

May result from :1.Very low amounts of vitamin K storage

2.No synthesis of vit. K in gut

sterile intestinal flora3. Absorption of vit K in gut very low

4. Disorder of vitamin K metabolism:

- Damaging of vit. K :barbiturat, phenytoin, diazepam, INH,Rifampisin

- disturbance of vit.K usage by liver:

dicumarol, salicylat


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FUNCTION OF VITAMIN K

Protein (II, VII, IX & X)

CarboxylationVitamin K

Functional of coagulation factor(II, VII, IX & X)

The process were done in liver

Incidence:


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Clinical manifestations:Bleeding in various location:

- gastrointestinal tract: melena

- umbilical cord, skin, mucosa- cephalhematom, brain bleeding

Incidence:- Age: 2 - 5 days

BLOOD HEMOSTASIS


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BLOOD HEMOSTASIS

ABNORMAL/PROLONGED NORMAL

PT (Factor II, VII, X)

APTT (Factor II, IX, X)

Thrombotest,Normotest (F. II, VII, X)

Activity F. II, VII, IX, X

There are PIVKA II

Thrombin time (TT)

Fibrinogen

Activity F. V, VIII, XI

Antigen F. II,VII,IX,X

Platelet count & BT

Practical:HDN: bleeding manifestation in baby


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TREATMENT

HDN self limited

Bleeding can stop spontaneously

but needs long time

- Massive hemorrhagic

- Continuous hemorrhagic- intracranial hemorrhagic

Threaten the newborns life

Needs immediate & the right treatment

HDN


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HDN

Vit. K 1-2 mg im/times

Anemia

PRC transf

Repeat Vit. K(3 times, every 6 hours)

-Continous bleeding orrecurrent

- Prolonged PTT

Plasma orFresh frozen plasma (FFP)

Plasma orfresh frozen plasma (FFP)

-Continous bleeding orrecurrent-Prolonged PTT

Severe hemorrhagicshock

20 ml/kgBW


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PROPHYLAXIS

Vitamin K 1 mg

High risk newborn :

- Premature

- Twins

- Assisted labor

- Asphyxia


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DIC

DISSEMIN TED INTR V SCUL R

CO GUL TION

- Intravascular coagulationspread

everywhere in blood vessel (systemic)

pathologic activation of

haemostatic mechanism

DIC:Defibrination syndrome = Consumption coagulopathy

complication: many condition / diseaseinitiate DIC

- WIDE ENDOTHEL DAMAGETISSUE THROMBOPLASTIN CIRCULATION


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- TISSUE THROMBOPLASTIN CIRCULATION

WIDE ACTIVATION OF

COAGULATION PROCESS

INTRAVASCULARTROMBI-FIBRIN

USAGE:- COAGULATION FACTOR- PLATELET

DEFICIENCY- COAGULATION FACTOR- PLATELET

HEMORAGE

FIBRINOLISIS

FDP

COAGULATIONDISORDER

BLOOD VESSELOCLUTION

ISCHEMIA

MAHA

ETIOLOGY:


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ETIOLOGY:

- Massive vascular endothel damage- Tissue Factor (tromboplastin) circulation

1. Trauma:

- burn, crush injury, heat stroke

2. Infection:

- Viral: DHF, Variola

- Bacterial: sepsis

- Fungus: candidiasis

3. Metabolic:

- Acidosis, alkalosis, ketosis

- Hyperthermia, hypothermia


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4. Immunologic:

- Blood transfusion reaction (massive hemolisis)

- Anaphylactic, Immune complex diseases.

5. Malignancy:

- Leukemia (ANLL-M3)

6. Others:- Shock

- Anoxia


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DIAGNOSIS

Primary Severe Disease

Duration of illness

with:- hemorrhage

- tissue/organ ischemia :

acral necrosisrenal failure

CLINICAL:


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- Blood smear microangiopathy:

burr cells, helmet cells

- Thrombocytopenia & prolonged bleeding time

- PT, PTT & prolonged thrombin time

-coagulation factor Fibrinogen

- FDP (FSP)

LABORATORY


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THERAPY

1. Treat etiology factor2. Blockade process

3. Blood/plasma component substitution

(14) hemorrhagic disease

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