Download - Coagulants and anti coagulants
![Page 1: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/1.jpg)
Coagulants & anti-coagulants
Dr. Karun Kumar JR-II
![Page 2: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/2.jpg)
• Haemostasis Limiting blood loss consequent to bleeding
• Homeostasis Maintenance of body’s internal environment within physiological limits
• Thrombus A clot that “adheres” to a vessel wall (Bad Blocks vessels)
• Embolus Intravascular clot that “floats” in blood
• “Detached” thrombus = Embolus
• Clot Good (Stops bleeding)
![Page 3: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/3.jpg)
Coagulation factorsFactor Common synonym
I Fibrinogen
II Prothrombin
III Tissue thromboplastin
IV Calcium
V Proaccelerin
VII Proconvertin
VIII AHF
IX Plasma thromboplastin component
X Stuart factor
XI Plasma thromboplastin antecedent
XII Hageman factor
XIII Fibrin stabilizing factor
![Page 4: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/4.jpg)
3 mechanisms of haemostasis
1. Vascular spasm (Damage to smooth muscle)
2. Platelet plug formation
3. Blood coagulation
![Page 5: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/5.jpg)
Intrinsic pathway
• Activated by surface contact with foreign body (Contact pathway)
• All factors and activators are contained within (intrinsic to) the blood
• Responsible for clotting when blood is kept in a glass tube (in vitro)
![Page 6: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/6.jpg)
Extrinsic pathway
• Activated by thromboplastin
• As a consequence of trauma, a tissue protein (tissue factor) leaks into the blood from cells outside (extrinsic to) blood vessels
• Rate limiting step in coagulation cascade activation of factor X (converging pathway)
![Page 7: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/7.jpg)
![Page 8: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/8.jpg)
PT aPTT
Intrinsicpathway interfered
Normal (12-14 secs)
Prolonged
Extrinsic pathway interfered
Prolonged (WEPT)
Normal (26-32 secs)
Common pathway interfered
Prolonged Prolonged
![Page 9: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/9.jpg)
Pro & anti-aggregatory factors
• Pro-aggregatory factor TXA2 (platelets)
↓ blood flow & ↑ platelet aggregation
• Anti-aggregatory factors
1. PGI2 Endothelial
2. NO cells
↑ blood flow & ↓ platelet aggregation
![Page 10: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/10.jpg)
![Page 11: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/11.jpg)
![Page 12: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/12.jpg)
![Page 13: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/13.jpg)
![Page 14: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/14.jpg)
Coagulants
• Indication Haemorrhagic states
• Best therapy Fresh whole blood / plasma
1. Vitamin K (K1 , K2 & K3) Cofactor in the post-translational carboxylation of glutamate residues on factors II, VII, IX, and X
2. Miscellaneous
• Fibrinogen
• Anti-haemophilic factor
• Desmopressin
![Page 15: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/15.jpg)
Anticoagulants
•Drugs that impede blood coagulation and prevent the occurrence or expansion of a thrombus
![Page 16: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/16.jpg)
Classification
1. Vitamin K antagonist Warfarin
2. Heparin & related drugs
a) Heparin
b) LMWH (Enoxaparin, Dalteparin, Tinzaparin)
c) Synthetic heparin derivatives (Fondaparinux – longer acting)
![Page 17: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/17.jpg)
3. Direct thrombin inhibitors
a) Parenteral Hirudin, Lepirudin, Argatroban,
Bivalirudin)
b) Oral Dabigatran
4. Active factor Xa inhibitor Rivaroxaban,
Apixaban
RIVAR Rivarsible (Reversible) ; O Oral;
XA X a ; BAN Blocker
![Page 18: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/18.jpg)
Warfarin (WEPT)
• Competitively inhibits vitamin K epoxide reductase & inhibits the posttranslational carboxylation of glutamate residues on vitamin K dependent coagulation factors II (prothrombin), VII, IX, and X
• Causes WAR during pregnancy
• PT should be monitored
![Page 19: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/19.jpg)
![Page 20: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/20.jpg)
![Page 21: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/21.jpg)
Heparin
• Antithrombin III Irreversibly inactivates thrombin & factor Xa
• Heparin potentiates anti-thrombin III activity
• Dosage determined by monitoring aPTT
![Page 22: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/22.jpg)
![Page 23: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/23.jpg)
![Page 24: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/24.jpg)
Advantages of LMWH
1. Can be administered s.c.
2. Effects are consistent & dosing less frequent (Long t1/2 & elimin. By 1st order kinetics)
3. Do not prolong aPTT & CT (Response is predictable & monitoring not required)
4. Dose is given in mg (not in units) can be easily calculated on body weight basis
5. Chance of haemorrhage chance is less
6. Risk of osteoporosis is decreased
![Page 25: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/25.jpg)
Heparin Warfarin
Route of admin.
I.v., S.c. Oral
Onset of action Immediate Delayed
Mechanism Activ. Of AT-III ↓ activ. Of c.f. 2,7,9,10
Antagonist Protamine sulphate
Vitamin K
Lab control aPTT PT
Drug interact. Few Many
Use To initiate therapy
For maintenance
![Page 26: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/26.jpg)
Uses of anti-coagulants
1. Prevention & t/t of DVT & PE
2. Myocardial infarction
3. Unstable angina
4. Rheumatic heart disease
5. Cerebrovascular disease
6. Haemodialysis
7. Defibrination syndrome (DIC)
![Page 27: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/27.jpg)
Antiplatelet drugs (ATD)
1. Aspirin
2. Cilostazol, Dipyridamole (PDE III inhib.)
3. P2Y12 receptor blocker
a) Reversible antag. Ticagrelor, Cangrelor
b) Irrev. Antag. Ticlopidine, Clopidogrel, Prasugrel
4. GP IIb/IIIa antag.
Abciximab, Tirofiban, Eptifibatide
![Page 28: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/28.jpg)
Aspirin
• It irreversibly inhibits
1. COX-1
2. TX-synthase
• It does NOT inhibit TXA2 directly
![Page 29: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/29.jpg)
Why low dose Aspirin ?
• 75-150 mg TXA2 formation suppressed
• > 900 mg ↓ PGI2 & TXA2
• TXA2 Platelets (Life span 5-7 days)
• PGI2 Endothelial cells
• Low dose (80-160 mg) Antiplatelet effect
• Moderate dose (650-975 mg) Analgesic & antipyretic effects
• High dose (3-6 g) Anti inflammatory effect
![Page 30: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/30.jpg)
![Page 31: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/31.jpg)
![Page 32: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/32.jpg)
• GP IIb/IIIa Protein complex on the surface of platelets.
• When activated, it aggregates platelets by binding to fibrin
![Page 33: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/33.jpg)
Summary
![Page 34: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/34.jpg)
Uses of anti-platelet drugs
1. MI Low dose Aspirin
2. Unstable angina Aspirin / Clopidogrel
3. Coronary bypass implants
4. Prosthetic heart valves
5. Arteriovenous shunts
6. Venous thromboembolism
7. Peripheral vascular disease
8. Cerebrovascular transient ischemic attacks
![Page 35: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/35.jpg)
Fibrinolytic drugs (USA)
• Lyse (dissolve) the thrombi (clots) in blood vessels by activating firbrinolytic system
1. Urokinase
2. Streptokinase
3. Anistreplase
4. Alteplase
5. Reteplase
6. Tenecteplase
![Page 36: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/36.jpg)
Mechanism of action
![Page 37: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/37.jpg)
Uses of fibrinolytics
1. Acute myocardial infarction
2. Deep vein thrombosis
3. Pulmonary embolism
4. Peripheral arterial occlusion
5. Stroke
![Page 38: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/38.jpg)
![Page 39: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/39.jpg)
Anti fibrinolytic drugs
1. Epsilon Aminocaproic acid
Blocks plasminogen activation (stops bleeding)
2. Tranexamic acid
Cyclic heavy menstrual bleeding
A/E Thrombosis
![Page 40: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/40.jpg)
Q.1. For each drug description, select the correct answer from the following choices:
(A)Eptifiatide (B) prasugrel (C) dabigatran
(D) Rivaroxaban (E) enoxaparin
1. This orally administered drug directly and selectively inhibits thrombin.
2. This drug produces irreversible blockade of platelet adenosine diphosphate P2Y receptors.
3. This orally administered inhibitor of active factor X (Stuart factor) is used to prevent DVT in persons undergoing hip-replacement surgery
4. This drug is a reversible fibrinogen antagonist at GP IIb/ IIIa receptors.
![Page 41: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/41.jpg)
Q.2. Which of the P2Y12 ADP receptor antagonists reversibly binds the receptor?
A. Clopidogrel
B. Prasugrel
C. Ticagrelor
D. Ticlopidine
![Page 42: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/42.jpg)
Q.3. A 70-year-old female is diagnosed with nonvalvular atrial firillation. Her past medical history is significant for chronic kidney disease, and her renal function is moderately diminished. All of the following anticoagulants would be expected to require a reduced dosage in this patient except:
A. Apixaban.
B. Dabigatran.
C. Rivaroxaban.
D. Warfarin.
![Page 43: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/43.jpg)
Q.4. An 80-year-old male is taking warfarin indefinitely for the prevention of deep venous thrombosis. He is a compliant patient with a stable INR and has no issues with bleeding or bruising. He is diagnosed with a urinary tract infection and is prescribed sulfamethoxazole/ trimethoprim. What effect will this have on his warfarin therapy?
A. Sulfamethoxazole/trimethoprim will decrease the anticoagulant effect of warfarin.
B. Sulfamethoxazole/trimethoprim will increase the anticoagulant effect of warfarin.
C. Sulfamethoxazole/trimethoprim will activate platelet activity.
D. Sulfamethoxazole/trimethoprim will not change anticoagulation status.
![Page 44: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/44.jpg)
Q.5 Which must heparin bind to in order to exert its anticoagulant effect?
A. GP IIb/IIIa receptor.
B. Thrombin.
C. Antithrombin III.
D. von Willebrand factor.
![Page 45: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/45.jpg)
Q.6. Which is most appropriate for reversing the anticoagulant effects of heparin?
A. Aminocaproic acid
B. Protamine sulfate
C. Vitamin K
D. Tranexamic acid
![Page 46: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/46.jpg)
Q.7. A 58-year-old business executive is brought to the emergency department 2 h after the onset of severe chest pain during a vigorous tennis game. She has a history of poorly controlled mild hypertension and elevated blood cholesterol but does not smoke. ECG changes confirm the diagnosis of myocardial infarction. The decision is made to attempt to open her occluded artery.
![Page 47: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/47.jpg)
I) Which of the following drugs accelerates the conversion of plasminogen to plasmin?
(A) Aminocaproic acid
(B) Heparin
(C) Lepirudin
(D) Reteplase
(E) Warfarin
![Page 48: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/48.jpg)
II) If a fibrinolytic drug is used for treatment of this woman’s acute myocardial infarction, which of the following adverse drug effects is most likely to occur?
(A) Acute renal failure
(B) Development of antiplatelet antibodies
(C) Encephalitis secondary to liver dysfunction
(D) Hemorrhagic stroke
(E) Neutropenia
![Page 49: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/49.jpg)
III) If this patient undergoes a percutaneous coronary angiography procedure and placement of a stent in a coronary blood vessel, she may be given eptifibatide. Which of the following most accurately describes the mechanism of eptifibatide anticlotting action?
(A) Activation of antithrombin III
(B) Blockade of post-translational modification of clotting factors
(C) Inhibition of thromboxane production
(D) Irreversible inhibition of platelet ADP rec.
(E) Reversible inhibition of GP IIb/IIIa receptors
![Page 50: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/50.jpg)
Q. 8. A 65-year-old man is brought to the emergency department 30 min after the onset of right-sided weakness and aphasia (difficulty speaking). Imaging studies ruled out cerebral hemorrhage as the cause of his acute symptoms of stroke.
![Page 51: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/51.jpg)
I) Prompt administration of which of the following drugs is most likely to improve this patient’s clinical outcome?
(A) Abciximab
(B) Alteplase
(C) Factor VIII
(D) Streptokinase
(E) Vitamin K
![Page 52: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/52.jpg)
II) Over the next 2 d, the patient’s symptoms resolved completely. To prevent a recurrence of this disease, the patient is most likely to be treated indefinitely with which of the following?
(A) Aminocaproic acid
(B) Aspirin
(C) Enoxaparin
(D) Lepirudin
(E) Warfarin
![Page 53: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/53.jpg)
Q.9. A 67-year-old woman presents with pain in
her left thigh muscle. Duplex ultrasonography indicates the presence of deep vein thrombosis (DVT) in the affected limb.
![Page 54: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/54.jpg)
I) The decision was made to treat this woman with enoxaparin. Relative to unfractionated heparin, enoxaparin
(A) Can be used without monitoring the patient’s aPTT
(B) Has a shorter duration of action
(C) Is less likely to have a teratogenic effect
(D) Is more likely to be given intravenously
(E) Is more likely to cause thrombosis and thrombocytopenia
![Page 55: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/55.jpg)
II) During the next week, the patient was started on warfarin and her heparin was discontinued. Two months later, she returned after a severe nosebleed. Laboratory analysis revealed an INR (international normalized ratio) of 7.0 (INR value in such a warfarin-treated patient should be 2.0–3.0). To prevent severe hemorrhage, the warfarin should be discontinued and this patient should be treated immediately with which of the following?
(A) Aminocaproic acid
(B) Desmopressin
(C) Factor VIII
(D) Protamine
(E) Vitamin K
![Page 56: Coagulants and anti coagulants](https://reader034.vdocuments.net/reader034/viewer/2022042716/55a7278f1a28ab925e8b4618/html5/thumbnails/56.jpg)
Q. 10. A patient develops severe thrombocytopenia in response to treatment with unfractionated heparin and still requires parenteral anticoagulation. The patient is most likely to be treated with which of the following?
(A) Abciximab
(B) Cilostazol
(C) Lepirudin
(D) Plasminogen
(E) Vitamin K1