Bleeding disorder

1. Dmlt class 6
BLEEDIND DISORDERS AND TEST

2. PHYSIOLOGY OF HEMOSTASIS
Hemostasis is the normal physiologic mechanism for
keeping the blood in fluid state in vascular system and
for prevention of hemorrhage by complex interaction
of blood vessel walls, platelets, and plasma proteins.
Following injury, initially vessel wall and platelets
interact to control hemorrhage by forminga platelet
plug at the site of injury; this is called as primary
hemostasis.
This is followed by activation of coagulation factors by a
series of enzymatic reactions to form a stable fibrin clot
(platelet plug enmeshed by fibrin); this is secondary
hemostasis.

3. Dissolution oftheclot will eventually occur by
fibrinolysis when healing is complete.
Hemostatic equilibrium requires normal blood vessels,
normal platelets, normal coagulation factors, normal
fibrinolysis, and normal coagulation inhibitor system.
3 main components of hemostasis-
1.BLOOD VESSELS
2.PLATELETS
3.COAGULATION FACTORS

4. Blood Vessel Wall
Transient constriction of blood vessels occurs at the site
of injury which helps to control blood los.
Endothelial cells synthesize von Willebrand factor
(vWF), tissue factor, and platelet activating factor,
which promote hemostasis.
subendothelial collagen is exposed which provides site
for attachment of platelets (adhesion).

5. Platelets
Platelets are produced by cytoplasmic fragmentation of
megakaryocytes in bone marrow.
Life-span of platelets is about 7-10 days.
Normal platelet count in peripheral blood is 1.5-4.0
lac/ul
About 2/3rd of platelets in the body arecirculating in
peripheral blood, while 1/3rd are pooled in spleen.
Main functions of platelets in hemostasis are adhesion,
release reaction, and aggregation.

6. Platelets attach to exposed subendothelium following
injury; this adhesion is mediated by vWF, which binds
to Gplb receptor on platelets.
platelets, which change shape from a disc to a sphere
and release their contents to the exterior (release
reaction).
Platelet aggregation refers to sticking of platelets to
each other; platelet agonists such as collagen, ADP,
thrombin, and TxA2 mediate aggregation.
Binding of ADP to platelets causes exposure of
Gpllb/1lla receptors which bind fibrinogen.
Fibrinogen binding to multiple platelets causes
formation of large platelet aggregates.

7. Adhesion Aggregation
Subendothelial collagen
Vascular wall
Dense
granule
-Endothelial
cell Platelet
wWF Alpha
granule
Lysosome
Gp Ib Platelet
receplor
Gplib/ilta
Fibrinogen
GP IIb/illa
Dense
granule >Platelet
receptor
Platelet Alpha
granule
Lysosomo
Platelet
Fig. 29.1: Platelet adhesion and aggregation

8. Coagulation Systeem
Normally, coagulation factors are circulating in an
inactive form.
Coagulation factors have been divided into thee groups
depending on similarities in structural and functional
properties:
(1) Fibrinogen group: 1, V,Vil,XIl;
(2) Vitamin-K dependent: 1, VIl, IX, X; and
(3) Contact group: XI, XIl, high molecular weight
kininogen, prekallikrein.

9. Coagulation System
Normally, coagulation factors are circulating in an
inactive form.
Coagulation factors have been divided into thee groups
depending on similarities in structural and functional
properties:
(1) Fibrinogen group: I, V, VIl1, XIll;
(2) Vitamin-K dependent:11,VII, IX, X; and
(3) Contact group: XI, XI, high molecular weight
kininogen, prekallikrein.

10. 010.1: Coaguiauontactors
Fibnnogen
Prothrombin
Liver Normal: 200-400 mg/dl; absent in serum
Vitamin K-dependent; multiple actions; absent in
dsorbed plasma
Activates coagulation through
extrinsic pathway
Acts asa cofactor in various
Liver
Tissue factor, Various tissues
thromboplastin
Calcium Obtained from
diet and bones coagulation reactions
Cofacto in conversion of
prothrombin to thrombin; abacnt in agod plaama
Labile factor Liver, platelets
There is no factor VI
Stable factor
Vil Liver
Anthemophilic globulin
antihemophiic factor
Christmas factor
Stuart-Prower factor
Vitamin K-dependent; absent in
adsorbed plasma; sensitive to
oral anticoagulant therapy
Two subunits: Vill:C and VIll:vWF; cofactor in the
conversion of F X to F Xa; absent in aged plasma
Vitamin-K dependent; absent in adsorbed plasma
Vitamin-K dependent; absent in adsorbed plasma
Liver
IX Liver
Liver
Plasma thromboplastin Liver Contact factor
antecedent
XI Hageman factor,
Contact factor
Contact factor; activates coagulation in vitro
deficiency does not cause bleedingg
Stabilizes fibrin clot by cross-linking fibrin
Liver
XI Fibnn stabilizing factor,
Lak-Lorand factor
Prekallik- Fletcher factor
Liver, platelets
monomers
Liver Contact factor: has many functions
rein
Contact factor: has many functions
High
molecular
Fitzgerald factor Liver
weight
kininogen

11. When activated, coagulation factors interact with
each other in a sequential manner to ultimately
form a fibrin clot and arrest bleeding.
Blood coagulation occurring in vitro is divided into
three pathways:
extrinsic,
intrinsic, and
Common

12. Extrinsic pathway
Extrinsic pathway
fntrinsic pathway
FVI
HMWK
FXI FXla TF
kalikrein
FVIL-TF complex
F X FXla
PL
Ca
FIX F IXa
F VII
PL
Ca
FX =FXa
FV
: PL
Ca
Prothrombin Thrombin
Common pathway
Fibninogen Fibrin
F XI
Cross-linkedfibrin
g
292 Normal coagulation mechanism. HMWK =
high molecular weight kininogen; PL =phospholipid; Ca =
calcium;
TF: tissue factor, solid arrow: conversion: Dotted arrow action; subscript a: activated form of the coagulation factor

13. BLEEDING DISORDERS
Tablo 29.2: Bleeding disorders
Disorders of blood vessels
Hereditary
Acquired
Allergic purpura
Infections: Gram-negative septicemia, viral infections
Scurvy
Senile purpura
Hereditary hemorrhagic telangiectasia
Disorders of platelets
Thrombocytopenia
Increased destruction of platelets
Idiopathic thrombocytopenic purpura
Defective platelet function
Acquired
Drugs: aspirnin, other nonsteroidal anti-inflammatory drugs,
ontibiotics, xylocainc
Myeloproliferative disorders
Infections: malania, dengue, septicemia, subacute
bactenial endocardtis, rubella, infectious mononucleosis
Drugs: quinidine. quinine, hepanin, procainamide
Heparin induced thrombocytopenia
Disseminated intravascular coagulation
Massive blood transfusion
Thrombotic thrombocytopenic purpura
Uremia
Paraproteinemia
Hereditary
Storage pool deficiency
Bernard-Soulier syndrome
Glanzmann's thrombasthenia
Alcohol
Toxemia of pregnancy
Increased pooling of platelets in spleen
Hypersplenism
Decreased production of platelets in bone marrow
Aplastic anemia
Bone marow infiltration: leukemias, lymphomas, myeloma
Megaloblastic anemia
Orugs
Infectons
Radiaio

14. Disorders of coagulation
Hereditary Acquired
Diaacminatod intravascular coagulation
Hemophilia A (F VIIl doficicncy)
von Willebrand's disease
Hemophilia B (F IX deficiency)
Disorders of fibrinogen
Liver disease
Vitamin K deficiency
Massive blood transfusion
Heparin or oral anticoagulant therapy
Renal disease
Paraproteinemia
Inhibitors of coagulation