Overview of hemostasis

antiplatelets, anticoagulants & fibrinolytic agents

Speaker: Dollasr.Huang
Date: 2020/04/27
 Arterial vs. Venous thrombosis

A. Arterial thrombosis occurs under high shear flow when platelet rich thrombi
are formed around ruptured atherosclerotic plaques and damaged endothelium.
B. Venous thrombosis occurs under low shear flow and mostly around intact
endothelial wall. Venous thrombi are fibrin rich, encapsulating a large amount of
red blood cells in addition to activated platelets.
Hemostasis
platelet aggregation & coagulation cascade

• Primary hemostasis
• platelet aggregation

• Secondary hemostasis
• coagulation cascade
 • Keywords：
• von Willebrand factor(vWF)
• Weibel Palade bodies(WPB) in

Platelate aggregation
endothelium
• α-granules in platelets
• GpIb-IX-V complex
• ADP receptor(P2Y1, P2Y12)
• P2Y1：Gq -> 增加Ca2+
• P2Y12：Gi -> 減少cAMP
• TXA2, PAF, calcium
• platelet GpIIb/IIIa R(integrin αIIbβ3)
Anti-platelet drugs
• irreversible COX inhibitor - Aspirin

• P2Y12 receptor antagonists(ADP-

R inhibitors)

• Clopidogrel(irreversible)

• Prasugrel(irreversible)

• Ticagrelor, Cangrelor(reversible)

• Ticlopidine [side effect:

neutropenia]

• Gp IIb/IIIa inhibitors

• Abciximab

• Eptifibatide

• Tirofiban

• May cause acute profound

thrombocytopenia [platelet
count < 50,000/mm3]
Anti-platelet drugs

• PDE inhibitor & adenosine uptake blockade

• Dipyridamole - combined with low-dose

aspirin (Aggrenox)

• Cilostazol (PDE3 inhibitor)

• Thrombin receptor(PAR-1) inhibitor

• Vorapaxar

• Atopaxar
 Anti-platelet drugs
Aspirin

• Effects

• COX-1 inhibition -> TXA2↓ -> antithrombotic effect【quickly onset, 7-10 days action duration】

• COX-1/COX-2 inhibition -> PGI2, PGE2↓ -> antipyretic, anti-inflammatory, and analgesic effect

• Indications

• AMI

• Acute ischemic stroke (given 24hrs after thrombolysis)

• Angina pectoris (stable/unstable)

• After revascularization procedures (to prevent stent thrombosis)

• Primary and secondary prevention of CVD

• symptomatic PAD

• Giant cell arteritis (to avoid blindness and/or stroke)

 Anti-platelet drugs
Aspirin

• Side effects

• Salicylate poisoning

• ↑ risk of ulcers, GI bleeding and perforation

• Aspirin exacerbated respiratory disease (AERD)

• pseudoallergic
• Samter’s triad: asthma, chronic/ recurrent rhinosinusitis, nasal polyps

• Reye syndrome
• Aspirin should be avoided in patients < 19 years of age, esp. in those
who have a febrile illness!
Coagulation cascade
• Keywords：
• Fibrinogen - Factor I
• Prothrombin - Factor II
• Extrinsic pathway
• Tissue factor(TF)
• Factor VII/VIIa
• PT
• Intrinsic pathway
• Factor VIII/IX/XI/XII
• aPTT
• Combined pathway
• Factor V/X/II/I
• PT/aPTT
• Factor XIII
 Anticoagulation
tissue factor pathway inhibitor(TFPI)
Anticoagulants PT/ INR aPTT

-xaban

Dabigatran
Warfarin
 Oral Anticoagulants
Indication

• Warfarin: Not suited for acute therapy of PE or DVT

• Valvular atrial fibrillation: arising from mitral stenosis with a significantly increased risk
of thromboembolism; Warfarin is the only approved treatment
• Antidotes:
• Dabigatran: idarucizumab (monoclonal antibody)
• Apixaban and rivaroxaban: andexanet alfa
• Oral anticoagulants is contraindicated in Pregnancy, esp. Warfarin!
 Oral Anticoagulants
Warfarin

• Side effects

• Dose-dependent increased risk of bleeding

• Extensive or life-threatening bleeding: stop coumarins; administer FFP or prothrombin

complex concentrate (PCC) and vitamin K

• Warfarin-induced skin necrosis

• Anticoagulants protein C and protein S are depleted more

quickly than procoagulants factors II, IX, and X -> increased factor V and VIII activity
-> initial hyper coagulable state -> vascular occlusion, tissue infarction, and blood
extravasation

• esp. when patient have protein C deficiency

• Prevention: temporary bridging therapy with heparin
• Regular monitoring of the PT/INR required [INR = 2.0-3.0]
 Parenteral Anticoagulants
Intro • Usually used for acute therapy of PE or DVT
• Can be used in pregnant women

In patients with antithrombin III deficiency (e.g., due to nephrotic syndrome), the effect is reduced
 Parenteral Anticoagulants
Heparin-induced thrombocytopenia (HIT)
Treatment with heparin, especially UFH, can cause thrombocytopenia.
Regular monitoring of platelet count is required!

Type 1 HIT Type 2 HIT

NO antibody involved IgG Ab against heparin-PF4 complex
Parenteral Anticoagulants
UFH vs. LMWH
 Parenteral Anticoagulants
Direct thrombin inhibitors (except Dabigatran)

• Drugs: argatroban, bivalirudin,

lepirudin/ desirudin
• Monitoring during therapy: aPTT
• Indications:

• Patients using heparin presented

with HIT - lepirudin & argatroban

• Thromboprophylaxis after elective

hip arthroplasty - desirudin

• HIT patients requiring PCI/CABG

- bivalirudin
 Fibrinolysis
tPA Indications
• Early STEMI (onset < 12hr ->
< 2hr PCI unavailable)
• Early ischemic stroke (<3hr)
• Massive PE from group A streptococci

Bleeding
Contraindications
• Prior intracranial hemorrhage
• Recent surgery
• Severe hypertension

Reversal of adverse effect

• Tranexamic acid
• Aminocaproic acid
• Fresh frozen plasma or
cryoprecipitate
D-Dimer

to r/o PE, DVT, DIC

教案關聯
• 教案中老張有⼼臟病史，做過PCI放了stent，合併有AF

• 因為要合併使⽤antiplatelet和anticoagulant的藥物，所以antiplatelet最好不要⽤
aspirin，常⽤的應該會是Clopidogrel

• Anticoagulant的部分，考慮病⼈的AF是valvular還是non-valvular，valvular⽤
Warfarin，non-valvular且經濟可負擔的話，就是⽤Xa inhibitor或Dabigatran

• ⽤Warfarin要檢測PT/INR