Download Coagulation

COAGULATION
HEMOSTASIS
Definition:
Hemostasis is the process of stopping blood loss.
This process occurs via the hemostatic mechanism known
as blood coagulation
Depend on :
1. VASCULAR PHASE
2. PLATELET PHASE
3. COAGULATION PHASE
4. FIBRINOLYTIC PHASE
VASCULAR PHASE:
WHEN A BLOOD VESSEL IS DAMAGED,
VASOCONSTRICTION RESULTS.
PLATELET PHASE:
PLATELETS ADHERE TO THE DAMAGED SURFACE AND
FORM A TEMPORARY PLUG.
COAGULATION PHASE:
THROUGH TWO SEPARATE PATHWAYS THE
CONVERSION OF FIBRINOGEN TO FIBRIN IS
COMPLETE.
FIBRINOLYTIC PHASE:
ANTICLOTTING MECHANISMS ARE ACTIVATED TO
ALLOW CLOT DISINTEGRATION AND REPAIR OF THE
DAMAGED VESSEL
HEMOSTASIS PROCESS
BV Injury
Tissue Factor
Neural
Blood Vessel
Constriction
Platelet
Aggregation
Coagulation
Cascade
Primary hemostatic plug
Reduced
Platelet
Activation
Blood flow
Stable Hemostatic Plug
Fibrin
formation
NORMAL CLOTTING
Response to vessle injury
1. Vasoconstriction to reduce blood flow
2. Platelet plug formation (von willebrand factor binds
damaged vessle and platelets)
3. Activation of clotting cascade with generation of fibrin
clot formation
4. Fibrinlysis (clot breakdown)
CLOTTING CASCADE
Normally the ingredients, called factors, act like a row of
dominoes toppling against each other to create a chain
reaction.
If one of the factors is missing this chain reaction cannot
proceed.
THE CLOTTING MECHANISM
INTRINSIC
EXTRINSIC
Collagen
Tissue Thromboplastin
XII
XI
VII
IX
VIII
X
FIBRINOGEN
(I)
V
PROTHROMBIN
(II)
THROMBIN
(III)
FIBRIN
HEMOSTASIS DEPENDENT
UPON:
-Vessel Wall Integrity
-Adequate Numbers of Platelets
-Proper Functioning Platelets
-Adequate Levels of Clotting Factors
-Proper Function of Fibrinolytic Pathway
Bleeding Disorders Causesed by
:
-VESSEL DEFECTS
-PLATELET DISORDERS
-FACTOR DEFICIENCIES
VESSEL DISORDERS
- VITAMIN C DEFICIENCY.
-BACTERIAL & VIRAL INFECTIONS.
-ACQUIRED & HEREDITARY CONDITIONS.
PLATELET DISORDERS
-THROMBOCYTOPENIA.
INADEQUATE NUMBER OF PLATELETS
-THROMBOCYTOPATHY.
ADEQUATE NUMBER BUT ABNORMAL FUNCTION
OTHER CAUSES
-HIV Virus
-Idiopathic Thrombocytopenia Purpura (ITP)
-Lymphoma
FACTOR DEFICIENCIES
(CONGENITAL)
-HEMOPHILIA A (Classic Hemophilia)
*Deficiency of Factor VIII
*80-85% of all Hemophiliacs
*Lab Results - Prolonged PTT
-HEMOPHILIA B (Christmas Disease)
*Deficiency of Factor IX
*10-15% of all Hemophiliacs
*Lab Results - Prolonged PTT
-VON WILLEBRAND’S DISEASE
*Deficiency of VWF & amount of Factor VIII
*Lab Results - Prolonged BT, PTT
OTHER DISORDERS
(ACQUIRED)
ORAL ANTICOAGULANTS
*COUMARIN
*HEPARIN
- LIVER DISEASE
-MALABSORPTION
-BROAD-SPECTRUM ANTIBIOTICS
HEMOPHILIA
Definition :
a medical condition in which the ability of the blood to clot is severely
reduced, causing the sufferer to bleed severely from even a slight
injury. The condition is typically caused by a hereditary lack of a
coagulation factor, most often factor VIII.
Clinical manifestations (hemophilia A & B are indistinguishable)
Hemarthrosis (most common)
Fixed joints
Soft tissue hematomas (e.g., muscle)
Muscle atrophy
Shortened tendons
Other sites of bleeding
Urinary tract
CNS, neck (may be life-threatening)
Prolonged bleeding after surgery or dental extractions
Vascular defect:

Infectious and hypersensitivity vasculitis
- Rickettsial and meningococcal infections
- Henoch-Schonlein purpura (immune)
THROMBOCYTOPENIA:
-DRUG INDUCED
-BONE MARROW FAILURE
-HYPERSPLENISM
-OTHER CAUSES
THROMBOCYTOPATHY:
-UREMIA
- INHERITED DISORDERS
- MYELOPROLIFERATIVE DISORDERS
- DRUG INDUCED
CLINICAL FEATURES
OF
BLEEDING DISORDERS
Platelet
disorders
Coagulation
factor disorders
Site of bleeding
Skin
Mucous membranes
(epistaxis, gum,
vaginal, GI tract)
Deep in soft tissues
(joints, muscles)
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,
usually mild
Delayed (1-2 days),
often severe
PLATELET
Petechiae:
COAGULATION
Hematoma.:
A SMALL RED OR PURPLE SPOT
A SOLID SWELLING OF
CAUSED BY BLEEDING INTO THE
CLOTTED BLOOD
SKIN
WITHIN THE TISSUES.
HEMARTHROSIS:
AN ACUTE
HEMARTHROSIS IS CHARACTERIZED BY RAPID JOINT
SWELLING THAT MAY BE PRECEDED BY A PRODROME OF REDUCED
RANGE OF MOTION AND PAIN.
HEMATOMA:
A SOLID
SWELLING OF
CLOTTED BLOOD
WITHIN THE
TISSUES.
PURPURA:
A RASH OF PURPLE SPOTS ON THE SKIN CAUSED BY
INTERNAL BLEEDING FROM SMALL BLOOD VESSELS
ECCHYMOSIS: (TYPICAL OF COAGULATION FACTOR
DISORDERS)
A DISCOLORATION OF THE SKIN RESULTING FROM
BLEEDING UNDERNEATH, TYPICALLY CAUSED BY
BRUISING.
Senile Purpura:
TYPICALLY AFFECTS ELDERLY
PATIENTS AS THEIR DERMAL
TISSUES ATROPHY AND BLOOD
VESSELS BECOME MORE FRAGILE.
PATIENTS DEVELOP PERSISTENT
DARK PURPLE ECCHYMOSIS,
WHICH ARE CHARACTERISTICALLY
CONFINED TO THE EXTENSOR
SURFACES OF THE HANDS AND
FOREARMS.
HENOCH-SCHONLEIN PURPURA:
(HSP) is a disease involving
inflammation of small blood
vessels. It most commonly
occurs in children. The
inflammation causes blood
vessels in the skin,
intestines, kidneys, and
joints . The main symptom is
a rash with numerous small
bruises, which have a raised
appearance, over the legs or
buttocks.
CT scan showing large hematoma
of right psoas muscle
VON W ILLEBRAND DISEASE: CLINICAL FEATURES
 Definition:
(VWD) is a bleeding disorder. It affects the blood's
ability to clot. If blood doesn't clot, can have
heavy, hard-to-stop bleeding after an injury. The
bleeding can damage the internal organs. Rarely,
the bleeding may even cause death.
Clinical features of (VWD):
The most common signs of (vWD) include
mucocutaneous bleeding like nosebleeds and
hematomas. Prolonged bleeding from trivial
wounds, oral cavity bleeding, and excessive
menstrual bleeding are common.
Gastrointestinal bleeding rarely occurs. Other
manifestations include the following :
CLINICAL FEATURES OF (VWD):
Easy bruising - Common but nonspecific
 Prolonged bleeding - After minor trauma to skin or
mucous membranes
 Severe hemorrhage - After major surgery; less common
 Delayed bleeding - May occur up to several weeks after
surgery
 Heavy bleeding - Common after tooth extraction or
other oral surgery, such as tonsillectomy and
adenoidectomy
 Menorrhagia - complaint in women
 Exacerbation of bleeding symptoms - After ingestion of
aspirin
 Amelioration of bleeding symptoms with use of oral
contraceptives

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
COMMON CLINICAL CONDITIONS ASSOCIATED WITH
DISSEMINATED INTRAVASCULAR COAGULATION
Activation of both coagulation and fibrinolysis
Triggered by

Sepsis

Obstetrical complications
Amniotic fluid embolism
 Abruptio placentae


Trauma
Head injury
 Fat embolism


Malignancy

Vascular disorders

Reaction to toxin (e.g.
snake venom, drugs)

Immunologic disorders
Severe allergic reaction
 Transplant rejection

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
MECHANISM
Systemic activation
of coagulation
Intravascular
deposition of fibrin
Thrombosis of small
and midsize vessels
with organ failure
Depletion of platelets
and coagulation factors
Bleeding
PATHOGENESIS OF DIC
Release of
thromboplastic
material into
circulation
Coagulation
LABORATORY EVALUATION
PLATELET COUNT
BLEEDING TIME (BT)
PROTHROMBIN TIME (PT)
PARTIAL THROMBOPLASTIN TIME (PTT)
THROMBIN TIME (TT)
Fibrinolysis
Fibrinogen
Plasmin
Thrombin
Fibrin
Monomers
Fibrin
Clot
(intravascular)
Fibrin(ogen)
Degradation
Products
Plasmin
Consumption of
coagulation factors;
presence of FDPs
 aPTT
 PT
 TT
 Fibrinogen
Presence of plasmin
 FDP
Intravascular clot
 Platelets
Schistocytes
THROMBOCYTOPENIA
Immune-mediated
Idioapthic
Drug-induced
Collagen vascular disease
Lymphoproliferative disease
Sarcoidosis
Non-immune mediated
DIC
Microangiopathic hemolytic anemia
LIVER DISEASE AND HEMOSTASIS
1.
2.
3.
4.
5.
6.
Decreased synthesis of II, VII, IX, X, XI, and fibrinogen
Dietary Vitamin K deficiency (Inadequate intake or
malabsortion)
Dysfibrinogenemia
Enhanced fibrinolysis (Decreased alpha-2-antiplasmin)
DIC
Thrombocytoepnia due to hypersplenism
COAGULATION
FACTOR DEFICIENCIES
SUMMARY
Sex-linked recessive
 Factors VIII and IX deficiencies cause bleeding
Prolonged PTT; PT normal
Autosomal recessive (rare)
 Factors II, V, VII, X, XI, fibrinogen deficiencies cause bleeding
Prolonged PT and/or PTT
 Factor XIII deficiency is associated with bleeding and
impaired wound healing
PT/ PTT normal; clot solubility abnormal
 Factor XII, prekallikrein, HMWK deficiencies
do not cause bleeding
BLEEDING TIME AND BLEEDING
 5-10%
of patients have a prolonged bleeding time
 Most
of the prolonged bleeding times are due to
aspirin or drug ingestion
 Prolonged
bleeding time does not predict excess
surgical blood loss
 Not
recommended for routine testing in
preoperative patients