Coagulation & Bleeding Problem

Fitria Nurul H
 HEMOSTASIS
• 1. VASCULAR PHASE
• 2. PLATELET PHASE
• 3. COAGULATION PHASE
• 4. FIBRINOLYTIC PHASE
 Lab Tests
Hemostasis •CBC-Plt
•BT,(CT)
BV Injury •PT
Tissue Factor •PTT
Neural

Blood Vessel Platelet Coagulation

Constriction Aggregation Cascade
Primary hemostatic plug

Reduced Platelet
Activation Fibrin
Blood flow formation
Plt Study
Morphology
Stable Hemostatic Plug Function
Antibody
So What Causes Bleeding Disorders?

VESSEL DEFECTS ?
PLATELET DISORDERS
FACTOR DEFICIENCIES
OTHER DISORDERS
?
 VITAMIN C
DEFICIENCY

VESSEL BACTERIAL & VIRAL

INFECTIONS
DEFECTS

ACQUIRED &
HEREDITARY
CONDITIONS
Vascular defect - cont.
Infectious and hypersensitivity vasculitis
- Rickettsial and meningococcal infections
- Henoch-Schonlein purpura (immune)
 THROMBOCYTOPENIA

PLATELET
DISORDERS
THROMBOCYTOPATHY
 THROMBOCYTOPENIA

INADEQUATE NUMBER
OF PLATELETS
 THROMBOCYTOPATHY
ADEQUATE NUMBER BUT
ABNORMAL FUNCTION
 Classification of platelet disorders
Quantitative disorders Qualitative disorders

Abnormal distribution Inherited disorders (rare)

Dilution effect Acquired disorders
Decreased production Medications
Bone marrow failure Chronic renal failure
Drug induced Cardiopulmonary bypass
Increased destruction
Hipersplenism
Drug induced
 Thrombocytopenia

Immune-mediated
Idiopathic
Drug-induced
Collagen vascular disease
Lymphoproliferative disease
Sarcoidosis
Non-immune mediated
DIC
Microangiopathic hemolytic anemia
• OTHER CAUSES
• Lymphoma
• Viral Infection (Dengue, Tiphoid, Leptospira,
HIV, dll)
• Idiopathic Thrombocytopenia Purpura (ITP)
 UREMIA

INHERITED DISORDERS
THROMBOCYTOPATHY
MYELOPROLIFERATIVE
DISORDERS

DRUG INDUCED
 Coagulation factor disorders

Inherited bleeding disorders Acquired bleeding disorders

Hemophilia A and B Liver disease
vonWillebrands disease Vitamin K
Other factor deficiencies deficiency/warfarin
overdose
DIC
FACTOR DEFICIENCIES
(CONGENITAL)

• HEMOPHILIA A

• HEMOPHILIA B

• von WILLEBRAND’S DISEASE

 FACTOR DEFICIENCIES
HEMOPHILIA A (Classic Hemophilia)
80-85% of all Hemophiliacs
Deficiency of Factor VIII
Lab Results - Prolonged PTT

HEMOPHILIA B (Christmas Disease)

10-15% of all Hemophiliacs
Deficiency of Factor IX
Lab Test - Prolonged PTT
 Hemophilia A and B
Hemophilia A Hemophilia B

Coagulation factor deficiency Factor VIII Factor IX

Inheritance X-linked X-linked

recessive recessive

Incidence 1/10,000 males 1/50,000 males

Severity Related to factor level

<1% - Severe - spontaneous bleeding
1-5% - Moderate - bleeding with mild injury
5-25% - Mild - bleeding with surgery or trauma

Complications Soft tissue bleeding

 Clinical manifestations (hemophilia A
& B are indistinguishable)

Hemarthrosis (most common)

Fixed joints
Soft tissue hematomas (e.g.,
muscle)
Muscle atrophy
Hemophilia Shortened tendons
Other sites of bleeding
Urinary tract
CNS, neck (may be life-
threatening)
Prolonged bleeding after surgery
or dental extractions
Hemarthrosis (acute)
 Intermediate purity plasma
products
Virucidally treated
May contain von Willebrand
factor
Treatment
High purity (monoclonal) plasma
of products
Virucidally treated
hemophilia No functional von Willebrand
factor
A
Recombinant factor VIII
Virus free/No apparent risk
No functional von Willebrand
factor
 Mild bleeding
Target: 30% dosing q8-12h; 1-2 days
(15U/kg)
Hemarthrosis, oropharyngeal or
dental, epistaxis, hematuria

Major bleeding
Dosing Target: 80-100% q8-12h; 7-14 days
(50U/kg)
guidelines for CNS trauma, hemorrhage, lumbar
puncture
hemophilia A Surgery
Retroperitoneal hemorrhage
GI bleeding

Adjunctive therapy
-aminocaproic acid (Amicar) or
DDAVP (for mild disease only)
Complications of therapy
Formation of inhibitors (antibodies)
10-15% of severe hemophilia A patients
1-2% of severe hemophilia B patients

Viral infections
Hepatitis B Human parvovirus
Hepatitis C Hepatitis A
HIV Other
 Treatment of hemophilia B

Agent
High purity factor IX
Recombinant human factor IX

Dose
Initial dose: 100U/kg
Subsequent: 50U/kg every 24 hours
FACTOR DEFICIENCIES
• VON WILLEBRAND’S DISEASE
• Deficiency of VWF & amount of Factor VIII
• Lab Results - Prolonged BT, PTT
 von Willebrand factor

• Synthesis in endothelium and megakaryocytes

• Forms large multimer
• Carrier of factor VIII

von • Factor VIII is bound to VWF while inactive in

circulation; factor VIII degrades rapidly when not
bound to VWF. Factor VIII is released from VWF by

Willebrand the action of thrombin. In the absence of VWF, factor

VIII has a half-life of 1-2 hours; when carried by
intact VWF, factor VIII has a half-life of 8-12 hour

Disease: • Anchors platelets to subendothelium

• Bridge between platelets

Clinical Inheritance - autosomal dominant

Features Incidence - 1/10,000

Clinical features - mucocutaneous

bleeding
 Laboratory evaluation of
von Willebrand disease
Classification
Type 1 Partial quantitative deficiency
Type 2 Qualitative deficiency
Type 3 Total quantitative deficiency

Diagnostic tests:

vonWillebrand type
Assay 1 2 3

vWF antigen  Normal 

vWF activity   
Multimer analysis Normal Normal Absent
 Cryoprecipitate

• Source of fibrinogen, factor VIII and VWF

• Only plasma fraction that consistently
contains VWF multimers
Treatment DDAVP (deamino-8-arginine
vasopressin)
of von •  plasma VWF levels by stimulating
secretion from endothelium
Willebrand • Duration of response is variable
• Not generally used in type 2 disease
Disease • Dosage 0.3 µg/kg q 12 hr IV

Factor VIII concentrate

(Intermediate purity)
• Virally inactivated product
 Vitamin K deficiency
Source of vitamin K Green vegetables
Synthesized by intestinal flora
Required for synthesis Factors II, VII, IX ,X
Protein C and S
Causes of deficiency Malnutrition
Biliary obstruction
Malabsorption
Antibiotic therapy
Treatment Vitamin K
Fresh frozen plasma
Clinical Features of Bleeding Disorders
Platelet Coagulation
disorders factor disorders
Site of bleeding Skin Deep in soft tissues
Mucous membranes (joints, muscles)
(epistaxis, gum,
vaginal, GI tract)
Petechiae Yes No
Ecchymoses (“bruises”) Small, superficial Large, deep
Hemarthrosis / muscle bleeding Extremely rare Common
Bleeding after cuts & scratches Yes No
Bleeding after surgery or trauma Immediate, Delayed (1-2 days),
usually mild often severe
 Platelet Coagulation

Petechiae, Purpura Hematoma, Joint bl.

Petechiae
(typical of platelet disorders)

Do not blanch with pressure

(cf. angiomas)
Not palpable
(cf. vasculitis)
Hemarthrosis
Hematoma
Petechiae
Purpura
Ecchymosis
Senile Purpura
Henoch-Schonlein purpura
Ecchymoses
(typical of coagulation
factor disorders)
CT scan showing large hematoma
of right psoas muscle
Common clinical conditions associated with
Disseminated Intravascular Coagulation
Activation of both coagulation and fibrinolysis
Triggered by
Sepsis Obstetrical complications
Amniotic fluid embolism
Trauma Abruptio placentae
Head injury
Vascular disorders
Fat embolism
Reaction to toxin (e.g.
Malignancy snake venom, drugs)

Immunologic disorders
Severe allergic reaction
Transplant rejection
Disseminated Intravascular Coagulation (DIC)
Mechanism
Systemic activation
of coagulation

Intravascular Depletion of platelets

deposition of fibrin and coagulation factors

Thrombosis of small Bleeding

and midsize vessels
with organ failure
Pathogenesis of DIC

Release of
thromboplastic
material into Consumption of
circulation coagulation factors;
presence of FDPs
Coagulation Fibrinolysis
 aPTT
 PT
Fibrinogen  TT
Plasmin
Thrombin  Fibrinogen

Presence of plasmin
Fibrin  FDP
Monomers Fibrin(ogen)
Degradation Intravascular clot
Products  Platelets
Fibrin Schistocytes
Clot
Plasmin
(intravascular)
Disseminated Intravascular Coagulation
Treatment approaches
Treatment of underlying disorder

Anticoagulation with heparin

Platelet transfusion

Fresh frozen plasma

Coagulation inhibitor concentrate (ATIII)

 OTHER DISORDERS
(ACQUIRED)

ORAL ANTICOAGULANTS
COUMARIN
HEPARIN
LIVER DISEASE
MALABSORPTION
BROAD-SPECTRUM ANTIBIOTICS
 Approach to bleeding disorders
Summary
Identify and correct any specific defect of
hemostasis
Laboratory testing is almost always needed to establish the cause of
bleeding
Screening tests (PT,PTT, platelet count) will often allow placement
into one of the broad categories
Specialized testing is usually necessary to establish a specific
diagnosis
Use non-transfusional drugs whenever possible
RBC transfusions for surgical procedures or large
blood loss