Coagulation Flashcards
Coagulation part II Bleeding
Coagulation part II Bleeding
What are the defects and genetic inheritance in the following illnesses…
von Willebrands disease?
Hemophilia A
Hemophillia B
Hemophillia C
von Willebrands disease >> vWF; auto dom or auto Rec
Hemophilia A >> VIII; X-linked
Hemophillia B >> IX: X-linked
Hemophillia C >> XI: auto recessive
What are the causes to the following acquired disorders…
Blood loss?
Excess anticoagulation?
Disseminated Intravascular Clotting?
Inhibitors?
Blood loss >> platelet and clotting factor depletion
Excess anticoagulation >> inhibition of clotting factors
Disseminated Intravascular Clotting >> platlet or clotting factor consumption; excess fibrinolysis
Inhibitors >> antibodies to clotting factor usu. VIII
What is glycoprotein 1b?
is a component of the GPIb-V-IX complex on platelets.
The GPIb-V-IX complex binds von Willebrand factor, allowing platelet adhesion and platelet plug formation at sites of vascular injury.
It is deficient in the Bernard-Soulier syndrome. A gain-of-function mutation causes platelet-type von Willebrand’s disease.
What is von Willibrand Disease?
Dec/ Absent or abnormal VW multimers
S/S epistaxis (nose bleed), bruising, menorrhagia, GI, gingival bleeding
Classified into 3 types
Dx: BT bleeding time, FVIII, VWAg, RIPA
Rx: DDAVP
VWF binds to VIII
DDAVP: (desmopressin acetate) are a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation.
What is Bernard Soulier Syndrome?
Deficiency of GP IB, Auto Recessive
Early childhood bruising, mucosal bleeding
Dx: Increased bleeding time, giant platelets, thrombocytopenia, Aggregation studies
Rx : platelets, DDAVP
What is Glanzmann’s Thrombasthenia?
See slide 50
Auto Recessive
Deficiency of glycoprotein IIb/IIIa
symptoms: early childhood bruising and bleeding
DX: bleeding time BT, platelet aggregation studies
What is glycoprotein IIb/IIIa?
In medicine, glycoprotein IIb/IIIa is an integrin complex found on platelets. It is a receptor for fibrin[1] and aids in platelet activation.
What is Virchow’s triad?
Endothelial injury
Abnormal blood flow
Hypercoagulability
What are the examples of endothelial injury?
Heart: endothelial injury adjacent MI, valvulitis
Atherosclerotic ulcerated plaques, vasculitis
Endothelial injury due to bacterial endotoxins, radiation, cigarette smoke products
End product: exposure of sub-endothelial collagen, platelet activation, adherence…..
What are examples in normal blood flow?
- Turbulance; arterial and cardiac thrombosis
- Stasis ; venous thrombosis
- Mechanisn:
- Disrupt laminar flow
- Prevent dilution of activated factors by fresh flowing blood
- Retard clotting factors inhibitors
- Promote endothelial cell activation
- Ulcerated atherosclerotic plaques, aneurysms-local stasis, MI, Mitral valve stenosis.
What is activated protein C resistance?
Activated Protein C cannot inactivate V, and V stays in circulation longer.
See below for details
AA replacement at one of three APC cleavage sites in the factor Va molecule
Factor V Leiden inactivated ~ ten times slower than normal factor V
Persists longer in the circulation results in increased thrombin generation and a mild hypercoagulable state
Individuals heterozygous for the factor V Leiden mutation have a slightly increased risk for venous thrombosis; homozygous individuals have a much greater thrombotic risk
What happens with a 20210 mutation?
causes increased prothrombin
increases risk for thrombosis
What are the main risk factors for Hereditary Thrombophillia?
(don’t need to know)
Factor V Leiden 30%
Prothrombin 8%
high homocysteine
What is Disseminated Intravascular Coagulation?
- pathologic, consumptive coagulopathy
- widespread, inappropriate coagulation leads to thrombosis of microvessels
- consumption of procoagulants and excess plasmin generation leads to hemorrhage
- Laboratory findings…
thrombocytopenia
prolonged screening coagulation tests
elevated D-dimer (fibrin degradation)
fragmented red blood cells (schistocytes)
What are the clinical causes of Disseminated Intravascular Coagulation?
bacterial sepsis, overwhelming viremia
trauma, tissue necrosis
some malignancies (esp. promyelocytic leukemia)
obstetric accidents
others
What is the treatment for DIC?
treat underlying condition
support with blood products
break DIC “cycle” with heparin (in some diseases)
What is heparin-induced Thrombocytopenia?
- Unfractionated heparin preparations
- Mechanism: generation of antibodies that bind Platelet Factor 4 PF4
- Antibodies bind to heparin-like molecules present on platelet surface and endothelium
- Platelet activation or endothelial injury occurs
- Prothrombotic state
- Tx: stop heparin
What is Antiphospholipid Antibody Syndrome aka Hughes Syndrome?
- Essentially, the pt can form clots anywhere
- Definition: Positive antiphospholipid antibody ; persistent, at least 6 weeks apart + 1 Clincial finding, such as
- Arterial or venous thrombosis
- Thrombocytopenia
- Frequent miscarriages
- Two classifications-
- Secondary APS; underlying autoimmune disorder, such as SLE (systemic lupus erythemia)
- Primary APS; No known underlying autoimmune disorder
Antiphospholipid Antibody Syndrome…
Mechanism?
Clinical Findings?
Dx?
Tx?
This is a long list. I doubt you need to know if.
Mechanism of hypercoaguable state: unknown
Direct platelet activation
Inhibition of PGI2 by endothelial cells
Inhibit functions of Protein C or S
CF : protean ; depending on vascular bed
Venous thrombosis: LE, Cerebral Vein, retinal
Neurologic disease: stroke , dementia
Preg complications: Miscarriages, HELLP
Hypoprothrombinemia
Diagnosis: Anticardiolipin Abs, Lupus inhibitor
Treatment: Warfarin, heparin, steroids
Summary:
Bleeding Disorders:
Vessel wall related abnormalities
Primary hemostasis (VW D, Bernard-Soulier, Glanzman Thrombasthenia
Secondary Hemostasis (Hemophilia, Christmas Disease)
Thrombosis- Virchows triad- endothelial abnormalities, hypercoagulable states
Summary:
Bleeding Disorders:
Vessel wall related abnormalities
Primary hemostasis (VW D, Bernard-Soulier, Glanzman Thrombasthenia
Secondary Hemostasis (Hemophilia, Christmas Disease)
Thrombosis- Virchows triad- endothelial abnormalities, hypercoagulable states
What are screening tests of Hemostatis?
- Personal/Family History/PE**
- First Level Testing:
- Platelets:
- Platelet count
- Bleeding Time
- Plasmatic Coagulation Factors
- Prothrombin time (PT)
- Activated Partial thromboplastin time(APTT)
