Download Document

Haemostasis
part2
ROLE OF ENDOTHILIUM
Hemostasis:
BV Injury
Tissue
Factor
Neural
Blood Vessel
Platelet
Coagulation
Constriction
Activation
Activation
Primary hemostatic plug
Reduced
Plt-Fusion
Blood flow
Thromibn,
Fibrin
Stable Hemostatic Plug
Coagulation:
Extrinsic-7
(PT)
Intrinsic 12,11,9,8
(aPTT-)
Common Path (TT)
FX  FXa
Prothrombin Thrombin
Fibrinogen  Fibrin
Clot formation & retraction
Fibrinogen
Thrombin
Fibrin Mononer
Fibrin Polymer
F-XIIIa
Cross Linked
Fibrin
Profibrinolytic
Procoagulant
Plasminogen
tPA
Fibrin Fragment D-dimer
Platelets
Factors
Fibrinogen
von Willebrand Factor
FORMATION
Anticoagulant
Antithrombin III
Protein C
Protein S
clot
RESOLUTION
Antifibrinolytic
PAI-1
Alpha-2 Antiplasmin
Role of thrombin
Coagulation Made Easy- The Mixing Study
• Useful to differentiate etiologies of
prolonged clotting in a coagulation assay.
• Patient’s plasma is mixed 50:50 with normal
plasma. Coagulation assay is repeated.
• If “substantial” correction is noted after mix,
suspect clotting factor deficiency.
• If no or minimal correction seen, suspect
inhibitor.
Disorders of the haemostatic mechanism are
devided into three main groups:
• Disorders of the vessels
• Disorders of the platelets
„ purpuric
diseases”
• Disorders of the coagulation mechanism
(„coagulopathies”)
The investigation of a patient with a suspected
disorder of haemostasis
– case history (personal details, family
history)
– inspection (type of bleeding)
– physical examination
– other known diseases
– drugs and medications
– laboratory tests
Certain signs and symptoms are virtually diagnostic of
disordered haemostasis.
The main symptom of all diseases is the bleeding:
● in the „purpuric disorders” cutaneous and mucosal
bleeding usually is prominent
● in different types of „coagulopathies” hemarthroses,
haematomas are the characteristic bleeding manifestations.
The onset of bleeding following trauma frequently is
delayed (recur in a matter of hours)
(the temporary hemostatic adequacy of the platelet
plug may explain this phenomenon).
Petechiae, purpuras:
small capillary haemorrhages ranging from the size of a pinhead to much larger
Petechiae, purpuras
Haematomas:
may be spontaneous (in a serious hemorrhagic disease) or may occur after
trauma (in a mild hemorrhagic disease).
Haematomas
Intramuscular injection may be very dangerous to
the patient with a bleeding disorder
Venipuncture (if skilfully
performed) is without danger
becouse the elasticity of the venous
walls.
Bleeding Disorders
Coagulopathies
• Aquired:
generally several coagulation
abnormalities are present.
Clinical picture is
complicated by signs and
symptoms of the underlying
disease.
Deficiencies of the vitamin K
dependent coagulation factors
(FII, VII, IX, X)
Hepatic disorders
Accelerated destruction of blood
coagulation (DIC)
Inhibitors of coagulation
Others (massive transfusion,
extracorporal circulation)
• Hereditary:
deficiency or abnormality of
a single coagulation factor.
–
–
–
–
Hemofilia A (FVIII)
Hemofilia B (FIX)
Von Willebrand’s disease
Rare coagulopathies
(FI. II. V. VII. X. XI. XIII)
Hereditary Factor Deficiencies
Hemophilia
• x-linked recessive conditions (males only)
• type A : F VIII:C deficiency (Classical Hemophilia)
B : F IX deficiency (Christmas disease)
C : F XI deficiency
• unexplained bruising or bleeding in young males,
usually ~ 1 yr of age
• joint & muscle bleeding → arthropathy
Haemophilia
A bleeding disorder in which clotting factor VIII
(eight) /Haemophilia A/ or IX (nine) /Haemophilia B/
in a person's blood plasma is missing or is at a low
level.
Prevalence:
haemophilia A: 105/million men
haemophilia B: 28/million men
• In haemophilia, VIII
or IX clotting factor is
missing, or the level of
that factor is low.
• This makes it
difficult for the blood
to form a clot, so
bleeding continues
longer than usual.
The hemophilia gene is carried on the X chromosome
 in males who lack a normal allele, the defect is manifested by
clinical haemophilia. Women may be carriers.
Haemophilia is a lifelong disease
• A person born with
haemophilia will have
it for life.
• The level of factor VIII
or IX in his blood
usually stays the same
throughout his life.
hemophilia A
Hereditary Factor Deficiencies
Hemophilia
■ screening: prolonged PTT
■ hemophilia A
mild
moderate
severe : life-threatening (CNS bleed)
• treatment
factor replacement
rFVIIa
Factor VIII Concentrate Necessary for Hemostasis
Factor VIII Concentrate
(% of normal)
Spontaneous hemorrhage
1-3 %
Moderate trauma
4-8 %
Hemarthrosis/deep skeletal
10-15 %
muscle hemorrhage
Major surgery
> 30%
Hemophilia B
(Christmas disease, Factor IX def.)
•less common than hemophilia A
•similar clinical Sx and inheritance
pattern as hemophilia A (sex-linked)
XII
XI
IX
VIII
VII
X
V
II
I
XIII
Stable clot
von Willebrand’s disease
• easy bruisability (no bleeding
into joints)
• unable to release VIII-vWF
• intact VIII-vWF synthesis
• VIII-C level is also decreased
(unknown reason)
• autosomal dominant
• 1 in 30,000 population
• usually diagnosed in
childhood or young adults
• increased bleeding time
• normal plt, PT
• normal or increased aPTT
Hereditary Platelet Disorder
von Willebrand Disease (vWD)
• most common congenital bleeding disorder
• quantitative or qualitative abn. of vWF
• Type 1: most common form
• partial quantitative deficiency of vWF
• autosomal dominant
• mucocutaneous bleeding
• hematology consult prior to surgery
• prolonged bleeding time, normal platelet
Hereditary Platelet Disorders
von Willebrand Disease (vWD)
Type 2: qualitative alterations in the vWF structure
& function
Type 3: least common and most severe
• Complete absence of vWF in plasma or storage organelle
• Autosomal recessive
• acquired vWD
• Lymphoproliferative disease ▪ cardiac/valvular disease
• Tumors
• Autoimmune disease
▪ medications (valproic acid)
▪ hypothyroidism
Hereditary Platelet Disorders
von Willebrand Disease
• Treatment: Desmopressin (DDAVP)
• synthetic analog of vasopressin
• ↑ both F VIII and vWF 3 - 5x in 30 mins
• preop prophylactic dose: 0.3 mcg/kg IV in 50 -100
ml NS infused 30-60 mins q 12-24 hrs PRN
• duration 8-10 hrs
• intranasal dose: 300 mcg – for home treatment,
not for preop prophylaxis
Hereditary Bleeding Disorders
von Willebrand Disease
• DDAVP
• vasomotor effect: flushing, ↑HR, headache
• SE: hyponatremia, seizures
• not for children < 3 yrs old
• unresponsive to DDAVP (15%)
• cryoprecipitate
• FFP
• factor VIII / vWF concentrate
Vitamin K Deficiency
vitamin K dependent factors : II, VII, IX, X
•acquired disorder
•may occur in
malnutrition,
malabsorption, biliary
obstruction, drug
•increased PT
•normal bleeding time, plt
•normal or increased aPTT
XII
XI
IX
VIII
VII
X
V
II
I
XIII
Stable clot
Severe Liver Disease
factors synthesized in liver : II, V, VII, IX, X, fibrinogen
XII
• increased PT, aPTT
• normal bleeding time, plt
XI
IX
VIII
VII
X
V
II
I
XIII
Stable clot
Platelet Dysfunction, Factor Deficiencies & Presence of
Inhibitors
• Liver disease
• synthesis of coagulation factors (except VIII),
anticoagulants, ATIII, protein C & S, plasminogen
• clearance of activated clotting factors, tPA, FDPs
• DIC
Blood Component Therapy
Transfusion of FFP
1) replacement of isolated factor deficiency
2) reversal of coumadin
3) antitrombin III deficiency
4) treatment of immunodeficiencies
5) treatment of TTP
6) massive blood transfusion
Blood Component Therapy
Cryoprecipitate
• contains significant levels of factor VIIIC,
factor VIII: vwF, XIII, fibrinogen
• indications:
1) hemophilia
2) von Willebrand disease
3) fibrinogen deficiencies
4) uremic platelet dysfunction
Coagulopathies
Disseminated Intravascular
Coagulation (DIC)
- an acute, subacute, or chronic thrombohemorrhagic disorder occurring as
a secondary complication in a variety of diseases
- activation of clotting system resulting in wide spread formation of
microthrombi throughout the microcirculation
- as a consequence, causing consumption of platelets, fibrin and coagulation
factors, and activation of thrombolytic mechanism
Two major triggering mechanisms
1. release of tissue factor or thromboplastic substance
2. widespread endothelial injury
DIC
Triggering Mechanisms
1. release of tissue factor or thromboplastic substance
- placental tissue
- granules from leukemic cells
- bacterial endotoxin
- mucus from adeno CA
2. widespread endothelial injury
- Ag-Ab immune complex deposit
- extreme temperature
- microorganisms
DIC
Pathology:
- wide spread thrombi
(brain, heart, lungs, kidneys, adrenals, spleen , liver)
- microinfarcts
Clinical:
- ~50% associated with obstetric complications
- ~30% with carcinomatosis
- microangiopathic anemia
- dyspnea, cyanosis
- convulsions, coma
- oliguria, acute renal failure
- shock, circulatory failure
DIC
Clinical:
acute DIC with a predominance of thrombin generation
and consumption of coagulation factors
bleeding tendency
(oozing from venopuncutres or operating site)
subacute and chronic DIC
thrombotic tendency