Hemostasis and Hemophilia

• Primary hemostasis forms the platelet plug.
• Secondary hemostasis is the coagulation cascade, which reinforces platelets with fibrin.
• Hemostasis operates through positive and negative feedback loops.
• Clotting factors are made in the liver.

Hemostasis

• Antithrombin inhibits thrombin and other coagulation factors, preventing excessive clotting.
• Fibrinolysis occurs through the action of plasmin, which breaks down fibrin.
• D-dimer indicates that fibrinolysis has occurred, as it is a breakdown product of cross-linked fibrin.
• Thrombus refers to a blood clot that forms inappropriately within a blood vessel or the heart
• Embolus is a thrombus that has broken loose and is travelling in the bloodstream.
• Arterial thrombi or white clots are made mostly of platelets.
• Venous thrombi or red clots are made mostly of fibrin and red blood cells.
• Hemostasis measurements determine the time it takes for blood to clot.

Hemophilia

• Hemophilia manifestations include prolonged bleeding, easy bruising, and joint bleeding.
• Hemophilia is typically caused by genetic mutations which affect the production of clotting factors.

DVT (Deep Vein Thrombosis)

• Three variables for DVT etiology include Virchow's Triad, hypercoagulability, stasis, and endothelial injury.
• Risk factors associated with DVT are immobility, surgery, trauma, cancer, pregnancy, and certain medications.
• Clinical manifestations of DVT include pain, swelling, warmth, and redness in the affected limb.
• DVT treatment involves anticoagulation, thrombolysis, and compression stockings.

Pulmonary Embolism

• PE can occur when a DVT breaks loose and travels to the lungs, lodging in the pulmonary arteries.
• Signs and symptoms of PE include shortness of breath, chest pain, cough, rapid heart rate, and dizziness.

Signs of Hemorrhage

• Signs of hemorrhage in patients taking antiplatelets, anticoagulants, or thrombolytics include unusual bruising, bleeding gums, blood in urine or stool, and severe headaches.

Antiplatelet Medications

Aspirin

• Aspirin's MOA involves inhibiting cyclooxygenase, preventing the production of thromboxane A2, a potent platelet aggregator.
• Aspirin's adverse effects include bleeding, gastrointestinal upset, and increased risk of ulcers.
• Aspirin's contraindications include hypersensitivity, active bleeding, and bleeding disorders.
• Clinical considerations for aspirin involve monitoring for bleeding and educating patients about the risks.

Clopidogrel

• MOA of clopidogrel involves blocking the ADP receptor on platelets, inhibiting platelet activation and aggregation.
• Clopidogrel's adverse effects consist of bleeding, thrombocytopenia, and hypersensitivity reactions.
• Clinical considerations for clopidogrel involve monitoring for bleeding and ensuring that patients are properly educated about the risks.

Eptifibatide

• Eptifibatide's MOA involves blocking the glycoprotein IIb/IIIa receptor on platelets, which inhibits platelet aggregation.
• Eptifibatide's adverse effects include bleeding, thrombocytopenia, and hypersensitivity reactions.
• Clinical considerations for eptifibatide involve administering intravenously and monitoring for bleeding.

Anticoagulants

• All anticoagulants decrease the production of fibrin.

Parenteral Anticoagulants

Unfractionated Heparin

• Unfractionated Heparin MOA involves activating antithrombin, which then inhibits thrombin and other coagulation factors.
• Adverse effects of Unfractionated Heparin consist of bleeding, heparin-induced thrombocytopenia (HIT), and hypersensitivity reactions.
• Contraindications of Unfractionated Heparin include active bleeding, severe thrombocytopenia, and hypersensitivity.
• Routes of Unfractionated Heparin are intravenous or subcutaneous.
• Monitoring Unfractionated Heparin involves the aPTT test.
• Protamine is the reversal agent for Unfractionated Heparin.

Heparin Induced Thrombocytopenia

• Suspect HIT when platelet count drops significantly after heparin administration.
• Treatment/interventions for HIT involve stopping heparin and administering a different anticoagulant.

Enoxaparin (LMWH)

• Enoxaparin (LMWH) MOA involves activating antithrombin.
• Enoxaparin (LMWH)'s adverse effects include bleeding, thrombocytopenia, and injection site reactions.
• Routes for Enoxaparin (LMWH) are subcutaneous.
• Dosing of Enoxaparin occurs 1-2 times per day
• Monitoring of Enoxaparin usually does not required.
• Protamine is the reversal agent for Enoxaparin.
• Enoxaparin should be administered subcutaneously into the abdomen

Oral Anticoagulants

Warfarin

• Warfarin's MOA includes interfering with the production of vitamin K-dependent clotting factors.
• Warfarin's adverse effects include bleeding, and skin necrosis.
• Warfarin's contraindications are pregnancy, active bleeding, and bleeding disorders.
• Drug interactions of Warfarin involve several medications and foods that can affect its efficacy.
• INR (International Normalized Ratio) is used to monitor Warfarin.
• Vitamin K is the reversal agent for Warfarin.
• Counseling points for patients on Warfarin include maintaining a consistent diet, monitoring for signs of bleeding, and taking medication as directed.
• There is a therapeutic delay with Warfarin use due to the time it takes to deplete existing clotting factors.
• Bridging refers to the use of a short-acting anticoagulant, such as heparin, to provide immediate anticoagulation while warfarin reaches therapeutic levels.

DOACs (Direct Oral Anticoagulants)

• Adjust dose and monitor all DOACs for renal and hepatic function.
• Dabigatran MOA is a direct thrombin inhibitor.
• The reversal agent for Dabigatran is idarucizumab.

"ban" drugs

• "ban" drugs MOA includes direct factor Xa inhibitors.
• The reversal agent of "ban" drugs is andexanet alfa.
• DOACs are mostly preferred over warfarin due to their predictable pharmacokinetics, rapid onset of action, and lower risk of bleeding.

Thrombolytic

Alteplase

• Alteplase's MOA involves converting plasminogen to plasmin, which then breaks down fibrin clots.
• Alteplase is indicated for treating acute ischemic stroke, pulmonary embolism, and myocardial infarction.
• Adverse effects of Alteplase consist of bleeding, and hypersensitivity reactions.
• Contraindications of Alteplase consist of active bleeding, recent surgery, and uncontrolled hypertension.
• Time-dependent effectiveness of Alteplase involves administering the drug as soon as possible after the onset of symptoms to maximize its benefits.