HAEMORRHAGIC DISEASE

HAEMORRHAGIC DISEASE

Suspected of hemorrhagic disease :

1. Spontaneous bleeding

2. Prolonged bleeding/massive 3. More than one site bleeding

Suspected of hemorrhagic disease :

1. Spontaneous bleeding

2. Prolonged bleeding/massive 3. More than one site bleeding

PATHOGENESISPATHOGENESIS

Hemostasis process :

- maintaining blood in a state of dilution - maintaining blood in vascular - to stop bleeding vascular damage

3 components of hemostasis:

HEMOSTASIS

VASCU

LAR

THROMBOCYTECLO

TTING

Disturbance one of components homeostasis bleeding

TRAUMA/INJURY

VASOCONSTRICTION

BLOOD

CLOTTING ADHESION OF THROMBCYTE

THROMBINE

FIBRINE

ADP/SEROTONINE

AGREGATION OF THROMBOCYTE

STABILE HAEMOSTATIC BLOCKAGE

+

DETECTION OF HAEMORRAGIC DISEASEDETECTION OF HAEMORRAGIC DISEASE

Step I - good history taking - physical examination

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

- Quantity and duration of bleeding - Recurrent bleeding

Step I - good history taking - physical examination

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

- Quantity and duration of bleeding - Recurrent bleeding

- 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

- 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

Laboratory examination :- Screening examination - Specific examination

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

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.

Specific examination : 1. Coagulation factor (factor assay) 2. Thrombocyte function : aggregation, release reaction etc.

VASCULAR DISORDERVASCULAR DISORDER

Mostly : secondary vascular pupura :

- Immunology: Schöenlein-Henoch syndrome - Infection: Virus, Rickets, Bacteria - Drugs - Deficiency of Vit. C - Uremia

Congenital: - Hereditary hemorrhagic telangiectasia

(Osler-Weber-Rendu)

- Cutis hyperelastica (Ehler-danlos)

Laboratory:

- platelet count normal

- bleeding time normal

- PT & APTT normal

Clinical : - usually petechiae skin & mucosa

spontaneous

- Tourniquet test positive

- symptoms & signs of primary disease

SCHöENLEIN-HENOCH SYNDROME SCHöENLEIN-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

-Hemolytic Streptococcal Infection important

- 75% cases History of respiratory tract

infection 1-3 weeks before

- 50% cases positive throat swab culture

- 30% cases titer ASO

PATHOGENESISPATHOGENESIS

Immune complex :- vasculitis increase permeability - perivasculer inflammation

CLINICAL MANIFESTATIONCLINICAL 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 - especially knee & ankle - full recovery

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

MANAGEMENTMANAGEMENT

self limiting symptomatic treatment

- Corticosteroid:- intestinal mucosa edema colic & invagination- arthricular involvement

- Bed rest avoid intracranial bleeding

- Good if no complication- Full recovery in 4 weeks- Residive

- Complication rare:- invagination, intestinal perforation- intracranial bleeding - renal failure

PROGNOSTICPROGNOSTIC

THROMBOCYTE DISORDERTHROMBOCYTE DISORDER

A. QUANTITATIVE DISORDER

1. Thrombocytopenia bleeding 2. Thrombocytosis thrombus formation

Normal:

platelet count 150.000 - 400.000/mm3

< 50.000/mm3 spontaneous bleeding

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

- Megaloblastic anemia- ANLL M7

b. Distribution disturbance:- Splenomegali: “pooling” thrombocyte- Lymphoma

c. Dilution:- Massive blood transfusion

THROMBOCYTOPENIA:THROMBOCYTOPENIA:

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

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

IDIOPATHIC/IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

IDIOPATHIC/IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

Destruction of platelet shorter age immunologic mechanism:

- antibody (IgG) platelet

- C3 complement

- cellular immunity activation: macrophage & cytotoxic cell

KLASIFIKASIKLASIFIKASI

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

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

- Umur : 2 - 8 tahun

- 50% kasus : 1 - 6 minggu sebelumnya viral infection: ARTI, hepatitis, mumps, mononucleosus infectiosa, cytomegaloviral etc.)

ITP AkutITP Akut

- perdarahan kulit dan selaput lender peteki dan ekimosis melena, hematuri

- peradarahan alat dalam jarang

- thrombositopeni berat perdarahan otak

- tourniquet test is positive

Gejala klinis:Gejala klinis:

- thrombositopeni- hapusan darah:

bentuk trombosit abnormal, ukuran besar, terpisah-pisah

- retraksi bekuan berkurang

- waktu perdarahan memanjang

- PT & APTT normal

Gambaran darah:Gambaran darah:

Penting menyingkirkan:- aplastic anemia- leukemia

Megakariosit:- Jumlah normal atau meningkat- Morfologi: - immatur - sitoplasma lebih basofil

- kurang granulasi

Sum-sum tulang:Sum-sum tulang:

- Istirehat dan hindari trauma

- Kasus ringan tidak perlu pengobatan

- Kasus berat perdarahan luas/berat:- kortikosteroid- suspense trombosit tidak dianjurkan- blood transfusion (PRC): atas indikasi

Pengobatan ITP akutPengobatan ITP akut

- Sebahagian besar (85 - 90 %) sembuh- 10 - 15% kronis

Prognosis:Prognosis:

ITP KronikITP Kronik

- Thrombositopeni (< 100.000/mm3) 6 bulan- Remisi spontan sangat jarang

- Umur > 10 tahun , Pr > Lk

Pengobatan:

1. Kortikosteroid

2. imunosupresif bila 1 tidak berhasil

3. IgG or Danazol

3. Sphlenektomy bila 1, 2 dan 3 tidak

berhasil

GANGGUAN PEMBEKUAN

Komponen pembekuan:

1. sistem Pembekuan Darah mekanisme pembekuan darah

2. Sistem Pencegahan Pembekuan mencegah pembekuan intravascular darah tetap cair

3. Sistem Fibrinolytic melisiskan fibrin lumen pembuluh darahtetap terbuka

Komponen pembekuan:

1. sistem Pembekuan Darah mekanisme pembekuan darah

2. Sistem Pencegahan Pembekuan mencegah pembekuan intravascular darah tetap cair

3. Sistem Fibrinolytic melisiskan fibrin lumen pembuluh darahtetap terbuka

SISTEM PEMBEKUAN DARAHSISTEM PEMBEKUAN DARAH

International NameSynonym

I Fibrinogen

II Prothrombin

III Tissue factor, Tissue thromboplastin

IV Calcium (Ca)

V Proacelerin, Labile Factor

VII Proconvertin, Stable factor

VIII Antihemophilic Factor, AHF-A

Faktor-faktor pembekuan darah:

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

SISTEM PEMBEKUAN DARAHSISTEM PEMBEKUAN DARAH

Inhibitor pembekuan:

- Antithrombin III - C Protein & S Protein

- Alpha-2 macroglobulin

Inhibitor pembekuan:

- Antithrombin III - C Protein & S Protein

- Alpha-2 macroglobulin

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

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

SISTEM PENCEGAH PEMBEKUAN: SISTEM PENCEGAH PEMBEKUAN:

SISTEM FIBRINOLITIK:SISTEM FIBRINOLITIK:

1.Pembentukan activator protrombin (Protrombinase):

- Intrinsic- Ekstrinsic

2. Prothrombin trombin

3. Fibrinogen fibrin

1.Pembentukan activator protrombin (Protrombinase):

- Intrinsic- Ekstrinsic

2. Prothrombin trombin

3. Fibrinogen fibrin

Proses pembekuan darah:Proses pembekuan darah:

Kontak permukaan

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++

Kerusakan jaringan

INTRINSIC

ExTRINSIC

1. Sistem pembekuan

2. Sistem pencegah pembekuan

3. Sistem fibrinolitik

GANGGUAN PEMBEKUANGANGGUAN PEMBEKUAN

Gangguan sistem/mekanisme pembekuan defisiensi satu atau lebih :

faktor pembekuan

1. Pembentukan berkurang:

- genetik/kongenital : hemophilia - Vit. K deficiency II, VII, IX & X, C Protein

- penyakit hati berat

1. Pembentukan berkurang:

- genetik/kongenital : hemophilia - Vit. K deficiency II, VII, IX & X, C Protein

- penyakit hati berat

2. PEMAKAIAN BERTAMBAH - Consumption coagulopathy Disseminated Intravascular Coagulation (DIC)

2. PEMAKAIAN BERTAMBAH - Consumption coagulopathy Disseminated Intravascular Coagulation (DIC)

1. Perdarahan trauma ringan, jarang spontan2. Jarang petechie3. Perdarahan sendi dan jaringan dalam

hematoma besar, ekimosis besar4. Perdarahan dari luka:

- tidak segera timbul - sering berulang - berlangsung lama (>48 jam) - merembes ( oozing )

Laboratorium:- PT & PTT: salah satu atau

keduanya - waktu perdarahan normal - observasi bekuan rapuh

Sifat-sifat gangguan pembekuan:Sifat-sifat gangguan pembekuan:

HEMOFILIAHEMOFILIA

HEMOFILIAHEMOFILIA

Penyakit perdarahn:

- Gangguan pembekuan Coagulation factors deficiency

- congenital, herediter

Hemophilia:Hemophilia A factor VIII deficiency

Hemophilia B factor IX deficiency

INSIDENINSIDEN

1 : 10.000 Hemofilia paling banyak

GENETIKA DAN PATOFISIOLOGIGENETIKA DAN PATOFISIOLOGI

- Factor VIII Gen X chromosome- Mutasi gen (substitusi dan delesi) gangguan sintesis faktor VIII

Penyakit diturunkan secara resesif Kromosom seks : X-linked

Male (Xh Y) affectedfemale (Xh X) carrier

Usually by marriage:

Normal father (X Y) Carrier mother (Xh X) Hemophilia almost entirely in boys

GENETICS AND PATHOPHYSIOLOGYGENETICS AND PATHOPHYSIOLOGY

F VIII: protein plasma are needed inprothrombin activator synthesis process

Women could be affected:- father = (Xh Y) & mother = (Xh X)- Inactive gene of VIII factor- Spontaneous mutation gene of VIII factor

F VIII deficiency coagulation cascade disturbance

GENETICS AND PATOPHYSIOLOGYGENETICS AND PATOPHYSIOLOGY

CLINICAL MANIFESTATION:CLINICAL MANIFESTATION:

Severe Hemophilia : F VIII < 1%spontaneous bleeding

hemarthrosis, muscle bleeding, gastrointestinal, hematuria & brain

Depends on F VIII levels

Moderate Hemophilia : F VIII 1 – 5 %bleeding after minor trauma

Mild Hemophilia : F VIII 6 – 25 %bleeding after major trauma,surgery

DIAGNOSISDIAGNOSIS

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

COMPLICATIONCOMPLICATION

hemophilia arthropathycontracture and paresis/paralysis of musclehemophilic pseudotumor

Formation antibody against F VIIIthrombosisITPViral hepatitis

Because of the disease:

Because of treatment:

TREATMENTTREATMENT

1. Stop the bleeding:Administration of F VIII:

- cryoprecipitate- F VIII concentrate (KOATE)

Bed rest Immobilizes bleeding area: cold compress, tampon

- Treatment of anemia & shock- synovectomy- joints & muscles rehabilitation

2. Correction of bleeding consequence:

3. Bleeding prevention:- prevention of trauma- addition of F VIII before surgery- contraindication: aspirin

TREATMENTTREATMENT

VITAMIN K DEFICIENCYVITAMIN 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 disease

3. Intestinal sterilization by antibiotics

HEMORRHAGIC DISEASE OF THE NEWBORN(HDN)

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 7 – 14 days of age

Physiology (normal):

Coagulation factor II,VII,IX & X:- decrease in newborn the lowest rate at 2 - 5 days of age

- increase at 7 – 14 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

Etiology:

- Uncomplete colonization of intestinal flora the synthesis of vit K in gut is still low

- decrease of vit K in placenta

If decreasing of coagulation factor excessive HDN

May result from :1.Very low amounts of vitamin K storage 2.No synthesis of vit. K in gut sterile intestinal flora

3. 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

May result from :1.Very low amounts of vitamin K storage 2.No synthesis of vit. K in gut sterile intestinal flora

3. 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

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

Clinical manifestations:

Bleeding in various location:- gastrointestinal tract: melena- umbilical cord, skin, mucosa- cephalhematom, brain bleeding

Clinical manifestations:

Bleeding in various location:- gastrointestinal tract: melena- umbilical cord, skin, mucosa- cephalhematom, brain bleeding

Incidence: - Age: 2 - 5 days

BLOOD HEMOSTASIS 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 <12 weeks with : - Prolonged of PT & APTT - Normal platelet and BT

TREATMENTTREATMENT

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

Vit. K 1-2 mg im/timesVit. K 1-2 mg im/times

AnemiaAnemia

PRC transfPRC transf

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

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

-Continous bleeding or recurrent- Prolonged PTT

-Continous bleeding or recurrent- Prolonged PTT

Plasma or Fresh frozen plasma (FFP)

Plasma or Fresh frozen plasma (FFP)

Plasma or fresh frozen plasma (FFP)

Plasma or fresh frozen plasma (FFP)

-Continous bleeding or recurrent -Prolonged PTT

-Continous bleeding or recurrent -Prolonged PTT

Severe hemorrhagic shock

Severe hemorrhagic shock

20 ml/kgBW

PROPHYLAXISPROPHYLAXIS

Vitamin K 1 mg

High risk newborn :

- Premature

- Twins

- Assisted labor

- Asphyxia

DICDIC= = DISSEMINATED INTRAVASCULAR DISSEMINATED INTRAVASCULAR

COAGULATIONCOAGULATION

DICDIC= = DISSEMINATED INTRAVASCULAR DISSEMINATED INTRAVASCULAR

COAGULATIONCOAGULATION

- Intravascular coagulation spread

everywhere in blood vessel (systemic) pathologic activation of haemostatic mechanism

DIC:Defibrination syndrome = Consumption coagulopathy complication: many condition / disease

initiate DIC

- WIDE ENDOTHEL DAMAGE - TISSUE THROMBOPLASTIN CIRCULATION

- WIDE ENDOTHEL DAMAGE - TISSUE THROMBOPLASTIN CIRCULATION

WIDE ACTIVATION OFCOAGULATION PROCESS

WIDE ACTIVATION OFCOAGULATION PROCESS

INTRAVASCULARTROMBI-FIBRIN

INTRAVASCULARTROMBI-FIBRIN

USAGE:- COAGULATION FACTOR- PLATELET

USAGE:- COAGULATION FACTOR- PLATELET

DEFICIENCY- COAGULATION FACTOR- PLATELET

DEFICIENCY- COAGULATION FACTOR- PLATELET

HEMORAGEHEMORAGE

FIBRINOLISISFIBRINOLISIS

FDP FDP

COAGULATIONDISORDER

COAGULATIONDISORDER

BLOOD VESSELOCLUTION

BLOOD VESSELOCLUTION

ISCHEMIAISCHEMIA

MAHAMAHA

ETIOLOGY: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

1. Trauma:- burn, crush injury, heat stroke

2. Infection:- Viral: DHF, Variola- Bacterial: sepsis- Fungus: candidiasis

3. Metabolic:- Acidosis, alkalosis, ketosis- Hyperthermia, hypothermia

4. Immunologic:

- Blood transfusion reaction (massive hemolisis)- Anaphylactic, Immune complex diseases.

5. Malignancy:- Leukemia (ANLL-M3)

6. Others:- Shock- Anoxia

4. Immunologic:

- Blood transfusion reaction (massive hemolisis)- Anaphylactic, Immune complex diseases.

5. Malignancy:- Leukemia (ANLL-M3)

6. Others:- Shock- Anoxia

DIAGNOSISDIAGNOSIS

Primary Severe Disease

Duration of illness with:- hemorrhage

- tissue/organ ischemia : acral necrosis

renal failure

Primary Severe Disease

Duration of illness with:- hemorrhage

- tissue/organ ischemia : acral necrosis

renal failure

CLINICAL:

- Blood smear microangiopathy:

burr cells, helmet cells

- Thrombocytopenia & prolonged bleeding

time

- PT, PTT & prolonged thrombin time

- coagulation factor Fibrinogen

- FDP (FSP)

- Blood smear microangiopathy:

burr cells, helmet cells

- Thrombocytopenia & prolonged bleeding

time

- PT, PTT & prolonged thrombin time

- coagulation factor Fibrinogen

- FDP (FSP)

LABORATORY

THERAPYTHERAPY

1. Treat etiology factor

2. Blockade process

3. Blood/plasma component substitution

1. Treat etiology factor

2. Blockade process

3. Blood/plasma component substitution