Platelets Flashcards
During platelet plug formation, what proteins trigger aggregation?
GPIIb-IIIa
What binds to vWF?
GPIb-IX-V
Where is vWF?
Endothelial cells
Order the intrinsic pathway
12–>11–>9 (+8) –> 10 (5) then common pathway
Order the common pathway
10 (+5) –> II (thrombin) –> I (fibrin) –> 13
Active Protein C inhibits
Factor 8 and 5
Not a necessary part of pathway
factor 12
measures intrinsic pathway
PTT
measures extrinsic pathway
PT
Thrombin activates
5, 7, 8, 11, 13 (almost all odds in a row except 8)
- *platelet aggregation
- **activates protein C pathway
How does protein C get activated?
- Thrombin (II) binds to thrombomodulin
- That complex binds to protein C
- Protein S then activates it
Heparin MOA
activates antithrombin
____ + _____ form mesh clot
fibrin (1) + factor 13
______ breaks up mesh clot once activated by ______
plasmin,
tPA and plasminogen
Antithrombin inhibits
Factor 10 and 2 (thrombin)
Why do we use PT to for warfarin monitoring when it inhibits factors in both pathways?
Factor 7, in the extrinsic pathway, had a short half life
3 roles of fibrin
- stabilize platelet plug
- induces platelet aggregation
- starts fibrinolysis process
Vitamin K dependent factors, warfarin inhibits
10 9 7 2 (year 1972)
CS
Dense granules contain
serotonin, ADP, Ca, ATP
Alpha granules contain
platelet growth factor, trans-growth factor beta, fibrinogen, vWF, platelet factor 4, factor V
Von-Willebrand Factor
large protein stored in endothelial cells/platelets
Functions:
1. bind to endothelium, promote platelet adhesion at injury site
2. plasma carrier for factor 8, prevents its degradation
Glycoprotein IIb/IIIa
fibrinogen receptor
GlycoproteinIb-IX
VWF receptor
Glycoprotein Ia/IIa
Glycoprotein VI
collagen receptor
Endothelial cells: Anticoagulant properties
- thrombomodulin binds thrombin, activates protein C
- Protein S
- tissue factor pathway inhibitors
- tissue plasminogen activator
- prostacyclin/nitric oxide inhibit aggregation
- Heparin activates antithrombin
Endothelial cells: Procoagulant properties
- injury
- down regulated thrombomodulin
- tissue factor expression
- PAI-1 expression
- vWF
PTT
Ref: 25-35 s
Intrinsic Pathway
*UFH monitoring
Reasons for prolonged PTT?
- Factor VIII or IX deficiency
aka hemophilia A/B - On heparin
PT
Ref: 10-14 s
Extrinsic Pathway
*warfarin monitoring
Reasons for prolonged PT?
- on warfarin
- vitamin K deficiency
- Amyloidosis: factor X bound up
- Homocystinuria: VII deficiency
Reasons for Vitamin K deficiency
drugs, newbown, low leafys, malabsorption, pancreatitis
Thrombin time
Ref: 14-16 s
good if on direct thrombin inhibitor
measures fibrinogen–>fibrin time
Vitamin K antagonist
warfarin
Factor Xa inhibitors
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Endoxaban (Savaysa)
LMWH
Enoxaparin (Lovenox)
Dalteparin (Fragmin)
Tinzaparin (Innohep)
Bernard-Soulier Syndrome
autosomal recessive
defect/loss platelet ADHESION receptors
thrombocytopenia
LARGE PLATELETS
Glanzmann Thrombasthenia
autosomal recessive
defect/loss receptors LINKING platelets
Storage Pool Defects
Lack DENSE granules, can’t package
Hermansky, Wiskott, Chediak Diseases
Aspirin-like defects
COX deficient, thromboxane synthetase deficient
Released and activates other platelets
Also inhibitied when taking ASA/NSAIDS
thromboxane
Gray Platelet Syndrome
abnormal ALPHA granule formation/secretion
smear is colorless w/o granules
Irreversible drugs
aspirin
clopidogrel
reversible drugs
NSAIDS 12-24 hours
Thrombocytopenia presentation
low platelets
mucous membranes bleed (epistaxis, gums, GI)
cerebral hemorrage
petechial rash
Destructive thrombocytopenia
-Ab mediated (ITP)
-Drug related (Heparin)
Splenomegaly/Hypersplenism (trapped)
Consumptive thrombocytopenia
- massive trauma
- dilutional (during transfusion of fluids)
- complicated surgery
- consume to stop bleeds
ITP
autoantibodies against antigen on platelet surface, eventual splenic destruction
ITP treatment
prednisone 3-6 months, IVIG if severe, then splenectomy if chronic
Drug related destruction
increased clearance and platelet destruction
Ab forms against drug and it cross reacts with platelets
-Antibiotics
-Heparin
HIT
hepatin + PF4 forms neoantigen on platelet surface
antibodies attack it
leads to hypercoaguability and clotting
Cases of hypoproliferation
BM fails to produce mature platelets 1. leukemia/lymphoma 2. metastatic CA 3. severe viral infection 4. radiation/chemo could get stem cell transplant
Causes of arterial thrombosis
platelet plug problem
- MI
- stroke
- peripheral artery vasculitis
- antiphos ab syndrome
- HIT
- hyperhomocyteinemia
Factor V Leiden
hypercoag-inherited
Factor V is resistant to active protein C
strong association with estrogen, stop OCPs
un-coagulate in pregnancy
Prothrombin gene mutation G20210A
hypercoag-inherited
upregulate prothrombin expression
cerebral vein thrombosis or stroke
Protein C deficiency
hypercoag-inherited
decreased synthesis and activitiy
warfarin skin necrosis
Protein S deficiency
hypercoag-inherited
decreased synthesis and activitiy
warfarin skin necrosis
HIT
Acquired thrombophilia
heparin induced clot- Ab mediated
switch to direct thrombin inhibitor in future
Antiphospholipid syndrome
Acquired thrombophilia Need one: recurrent miscarraige, VTE, MI, microvascular thrombosis w/ multi organ failure Need two 12 week apart: 1. Lupus anticoag 2. anticardilipid Ab 2. B2 glycoprotein Ab
Antithrombin deficiency
hypercoag-inherited
heparin resistance, low antithrombin
VTE Risk factors
immobilization personal/family history unexplained miscarriages cigarettes OCPs cancer recent surgery central venous catheter trauma heparin exposure
Fibrinolysis
conversion of plasminogen to plasmin mediated by tissue plasminogen activator (tpa)
Virchow’s Triad
Endothelial injury
venous stasis
hypercoagability
(perfect situation for a clot!)
DVT long term complication
post thrombotic syndrome: perm venous valve damage and long term swelling
PE long term complications
thromboembolic pulmonary HTN
greater risk of death than DVT
DVT symptoms
Homan’s sign
pain, swelling, tender
palpable cord
prominent superficial veins
PE symptoms
SOB, tachycardia, pleuritic chest pain, cough, hemopytsis, hypotension, syncope, death, R side heart failure
VTE treatment steps
- anticoagulate acutely (UFH/LMWH/DOAC)
- risk-stratify for thrombolysis (tPA)
- convert to chronic anticoagulants (warfarin/DOAC)
Bridging to warfarin
d/t hypercoaguable state at start, overlap with UFH/LMWH until PT/INR is therapeutic
Contraindications for warfarin
IVC filter
Diagnosing PE
VQ Scan: ventilation normal, perfusion altered
PECT w/ contract
Treatment for mild hemophilia
DDAVP
Prior to surgeries
Releases factor 8 stores
Hemophilia A only
Inherited causes of prolonged PTT
VWF
Factor VIII, IX, XI, XIII deficiencies
Acquired causes of prolonged PTT
Heparin
Antiphospholipid antibody
Inherited causes of prolonged PT
Factor VII deficiency
Acquired causes of prolonged PT
Vit K deficiency
Liver disease
Warfarin
Factor VIII inhibitor
Inherited causes for prolonged PT and PTT
Prothrombin, fibrinogen, factor V, factor X, or combined factor deficiencies
Acquired causes of prolonged PT and PTT
Vitamin K deficiency Liver disease DIC**** Supratherapeutic heparin or warfarin Combined heparin or warfarin use Direct thrombin inhibitors Inhibitor of prothrombin, fibrinogen, or factored V or X
Oozing at venapuncture site could indicate
K deficiency
How does liver disease cause coagulopathy?
It has decreased production of clotting factors
(Factor 8 and vWF are not made in liver)*
