Hemostasis Flashcards
What are the functions of platelets?
1- adhesion to damaged sub endothelium 2- primary aggregation -> PG E2, F2, TXA2 3- secretion of: - serotonin -> vasoconstriction - ADP -> secondary aggregation - PF3 -> coagulation - Retactozyme 4- secondary aggregation by ADP - maintained by GpIIb/IIIa that binds fibrinogen
When is the decrease of platelets noticed clinically?
- clinical petichae < 50 000
- serious bleeding < 20 000
What is the body’s natural coagulation system?
Extrinsic pathway
- factor 7 ——–> 10
Intrinsic pathway
- factor 12 -> 11 -> 9 -> 8 ——-> 10
Common pathway
- 10 -> 5 -> prothrombin to thrombin -> fibrinogen to fibrin
what is the body’s natural anticoagulation system?
1- intact endothelium -> prostacyclin & plasminogen activator
2- protein C & S -> C inhibits factor 5 & 8
3- Heparin cofactor II
4- tissue factor inhibitor -> extrinsic pathway
5- fibrinolytic system -> tPA
6- anti thrombin III
7- clearance of clotting factors by liver
What are the manifestations of defect in blood vessels or platelets?
- skin -> petichea <3mm -> flat in platelet defect & raised edges in BV defect
- mucous membranes -> epistaxis, bleeding gums, hematuria, hemoptysis
- internal organs -> cerebral hemorrhage
- spontaneous bleeding if platelets < 20 000
What is the clinical picture in case of coagulation system defect?
- skin -> ecchymosis, hematoma
- deep bleeding -> muscles & joints
- external bleeding -> hematemesis, hematuria, hemoptysis
- prolonged bleeding after cutting umbilical cord & circumcision
What are the investigations performed to differentiate between causes of bleeding?
1- BV & platelet defect 2- platelet defect 3- coagulation defect 4- anemia 5- investigations foe the cause
What are the investigations that reveal BV/platelet defects?
BV & platelets
- Bleeding time -> 2 - 4 min normally
- Hess capillary fragility test -> inflate sphygnomanonmeter 80mmHg every 5 minus -> < 5 petichae may be seen normally
Platelets
- spontaneous bleeding < 20 000
- platelet function -> aggregation & adhesion by aggregometer & ADP content/PF3 activity
What are the investigations that reveal a coagulation defect?
- clotting time: 5 - 10 mins normally
- PTT -> 30 - 40s normally (common & intrinsic pathways)
- PT -> 14s normally (common & extrinsic pathways)
- INR -> patient PT/control PT
- assay of serum level of clotting factors
What are the causes of vascular purpura?
Hereditary
1- hereditary hemorrhagic telangiectasia
-> autosomal dominant with impaired vasoconstriction
- treatment: Epsilon amino caproic acid
2- connective tissue disorder
- Ehler Danlos -> hyperlaxity
- Marfan syndrome -> aortic regurgitation & tall stature
Acquired
1- traumatic -> convulsions, malignant hypertension, cough
2- inflammatory -> Purpura fulminants, rickets, SLE, PAN
3- immunological -> anaphylactoid purpura
4- idiopathic -> Devil’s punch
5- mesynchymal weakness
- scurvy -> defective collagen synthesis due to vit C deficiency
- steroid & Cushing’s -> diminished collagen synthesis
- senile purpura
What is the etiology of anaphylactoid purpura?
allergic reaction to strep throat -> formation of immune complex (IgA + And + complement) -> capillaritis & arteriolitis
What is the clinical picture pf anaphylactoid purpura?
- petichae on buttocks
- arthralgia -> tender swollen joints
- nephritic syndrome
- GI bleeding
How is anaphylactoid purpura diagnosed & treated?
- increased bleeding time
- Hess capillary fragility test
- anemia from bleeding
- renal function impairment & RBC casts
- autoantibodies
treatment
- corticosteroids
- symptomatic treatment
What are the causes of platelet defect purpura?
1- increased destruction -> hypersplenism, immunological
2- decreased production -> aplastic anemia, megaloblastic anemia, thiazides & imipenam
3- pooling -> splenomegaly & hypothermia
4- dilutional -> massive blood transfusions
5- increased consumption -> DIC
What is the etiology of ITP?
autoimmune disease characterized by IgG (ITP factor) -> antibodies that
- increase removal of platelet by RES
- decrease budding of megakaryocytes
could be associated with SLE, CLL, autoimmune hemolytic anemia
What is the presentation of ITP?
ACUTE
- in children 2-9 years
- spontaneous remission
CHRONIC
- 20 - 40 years
- females
- remission & exacerbation
Clinical picture of purpura due to platelet defect
- skin & mucous membranes -> epistaxis, gum bleeding, petichae
- organs -> hematuria, hemoptysis, cerebral hemorrhage
- spontaneous bleeding < 20 000
What will be found on investigation of ITP?
- increased bleeding time & + capillary Hess test
- decreased platelet count
- anemia
- auto antibodies +ive
How is ITP managed?
1- general measures -> avoid injury, trauma, surgery, & aspirin
2- steroids -> prednisone
3- immunosuppressive -> cyclophosphamide or azathiopnire
4- splenectomy -> in case of
- failed steroid therapy
- relapse after stopping steroids
- fulminant cases
5- IV IgG to block receptors of macrophages -> in emergencies only
6- plasmapheresis
What is thrombocytosis & what are its causes?
platelets > 400 000
Primary
- essential thrombocytosis
- polycythemia vera
- CML
- myelofibrosis
Secondary
- post splenectomy
What is the clinical picture & treatment of thrombocytosis?
CP
- thrombosis (increased platelets) + bleeding (defective platelet function)
Treatment
- hydroxyurea
- busulphan
- alpha-interferon
- treat the cause
What are the causes of coagulation defects?
HEREDITARY
- Hemophilia A -> factor 8
- Hemophilia B -> factor 9
- Parahemophilia -> factor 5
- Afibrinnogenemia -> factor 1
ACQUIRED
- Liver failure -> decrease in coagulation factors
- Renal failure -> accumulation of toxins affects protein synthesis
- Vitamin K deficiency -> defect in factors 1972
- DIC -> consumption of coagulation factors & platelets
- Drugs -> heparin
- SLE
- Hypothermia
What is the etiology & clinical picture of hemophilia A?
- X-linked recessive disease -> mostly affects men
- deficiency in factor VIII (8)
- always positive family history
- females are carrier
- most common CP -> hematoma & hemoarthrosis
What are the investigations done for hemophilia A?
- bleeding time, capillary fragility test & platelet count are normal
- prolonged PTT -> because intrinsic pathway is affected (factor 8)
- PT & TT are normal
- decreased factor VIII level
- microcytic hypochromic anemia
How is hemophilia A treated?
1- replace factor VIII -> cryoprecipitate (factor VIII & fibrinogen II)
- FFP or blood
- AHF concentrates
2- Desmopressin -> increases release of factor VIII from endothelium
3- in case of Hemoarthrosis -> physical therapy, analgesia, & aspiration after givinng factor VIII
4- prophylaxis
- genetic counseling
- avoid trauma, unnecessary operations, anticoagulants, & aspirin
- immunization against hepatitis & tetanus
- AHG prophylaxis before surgery
What is the difference between hemophilia A & B?
Hemophilia B
- deficiency in factor 9
- treated with plasma & factor IX concentrate
all the rest is the same
What is the etiology for vitamin K deficiency?
1- Decreased intake 2- decreased flora synthesis - premature infants - prolonged intake of oral antibiotics 3- decreased absorption - obstructive jaundice - malabsorption syndrome 4- decreased activation - liver cell failure - oral anticoagulants
What is the clinical picture of vitamin K deficiency?
like hemophilia but without hemoarthrosis
- skin -> ecchymosis & hematoma
- internally -> bleeding in muscles & brain
- externally -> hematemesis, hemoptysis, hematuria
- anemia
- CP of the cause
How is vitamin K deficiency diagnosed with investigations?
- normal bleeding time, Hess capillary fragility test, & platelet count
- Clotting time, PTT, & PT are PROLONGED
- assay of coagulation will show decreased factors 10, 9, 7, 2
How is vitamin nK deficiency managed?
- IV vitamin K
- or plasma transfusion
- treat the cause -> stop anticoagulants
What is the presentation of DIC?
Thrombosis
- thrombosis -> ischemia & organ failure
- formation of fibrin network is circulation -> intravascular hemolysis
Bleeding
- platelet consumption
- coagulation factor consumption
- FDP increase -> more bleeding
What are the causes of DIC?
- obstetric cause
- cancer prostate
- major surgery
- incompatible blood transfusion
- sepsis or other types of shock
- fat embolism
- burns
- liver cell failure
What is the clinical picture of DIC?
1- Tissue ischemia - ARDS - Respiratory failure - liver failure - peripheral ischemia 2- Bleeding 3- C/P of cause
What will be found on investigation of DIC?
everything is increased except fibrinogen & platelet count
- bleeding time, + Hess capillary fragility test
- prolonged clotting time, PT, & PTT
- decreased fibrinogen but increased FDPs
- thrombocytopenia (decreased platelets)
- intravascular hemolysis -> decreased heptaglobin & hemipixin
- organ failure
- all coagulation factors decreased
What is the treatment of DIC?
depending on the dominant symptom if its bleeding or thrombosis
if BLEEDING -> replace coagulation factors only
1- plasma only
2- platelets if count is < 20 000
3- cryoprecipitate
4- epsilon aminocaproic acid & tranexamic acid in case of profuse bleeding
if THROMBOSIS
- give heparin ONLY if bleeding is NOT from major vessels
