Charlie Colquitt,BS,PharmD,CPh

Transcription

1 Charlie Colquitt,BS,PharmD,CPh Associate Professor of Pharmacy Practice Florida A & M University, Tampa Bay Center Clinical Pharmacist Community Health Centers of Pinellas, Inc. June 18 th, 2015

2 I, do not have a vested interest in or affiliation with any corporate organization offering financial support or grant money for this continuing education program, or any affiliation with an organization whose philosophy could potentially bias my presentation.

3 At the end of this presentation, the participant should be able to: Describe the process of hemostasis and thrombosis Discuss the pathogenosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) Identify a patient s risk of developing venous thrombosis Recognize the signs and symptoms of DVT and PE Describe the novel anticoagulant options indicated for VTE Discuss the management of bleeding

4 At the end of this presentation pharmacy technicians should be able to: Define DVT and PE Identify the novel anticoagulant options

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6 Diagnosed VTE at 2 to 3 per 1000 Incidence increases with age Estimated incidence of 8 per 1000 in those over 80 years. High incidence in patients with multiple traumas, orthopedic procedures Prior history of VTE Metastatic cancer Post MI, stroke, spinal cord injury Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

7 Stasis of blood The rate of blood flow is slow in the lower extremities. Contraction of the calf and thigh muscles work with valves in the deep veins of the leg to facilitate blood flow Vessel obstruction External compression or a thrombus promotes clot aggregation Hypercoagulability Inherited disorders Yusen R, Eby C, Gage B. Disorders of hemostasis and thrombosis. In:Foster C, Mistry N, Peddi P. The Washington Manual of Medical Therapeutics. 33 rd ed. Philadelphia, Pa: 2010.

8 Platelet Plug Formation On vascular injury, platelets adhere to the site of injury. Platelet adhesion results in subsequent activation and aggregation. During platelet aggregation, additional platelets are recruited from the circulation to the site of vascular injury, leading to the formation of an occlusive platelet thrombus. The platelet plug is anchored and stabilized by the developing fibrin mesh. Yusen R, Eby C, Gage B. Disorders of hemostasis and thrombosis. In:Foster C, Mistry N, Peddi P. The Washington Manual of Medical Therapeutics. 33 rd ed. Philadelphia, Pa: 2010.

9 Clotting factors normally circulate inactive. Two pathways of blood coagulation: extrinsic and intrinsic. Coagulation is initiated by tissue factor (TF) exposure. TF with FVIIa, activates FIX and FX. FIXa binds to FVIII activating FX to form FXa. FXa binds FV which converts prothrombin to thrombin. Thrombin activates FXIII that cross-links fibrin to form a stabilized clot. Yusen R, Eby C, Gage B. Disorders of hemostasis and thrombosis. In:Foster C, Mistry N, Peddi P. The Washington Manual of Medical Therapeutics. 33 rd ed. Philadelphia, Pa: 2010.

10 The intact endothelium adjacent to the damaged tissue actively secretes several antithrombotic substances. Thrombomodulin causes protein C to convert to its active form activated protein C (apc). When joined with its cofactor protein S, apc inactivates FVa and FVIIIa regulating coagulating complexes. Antithrombin (or antithrombin III) neutralizes thrombin Tissue factor pathway inhibitor (TFPI) Yusen R, Eby C, Gage B. Disorders of hemostasis and thrombosis. In:Foster C, Mistry N, Peddi P. The Washington Manual of Medical Therapeutics. 33 rd ed. Philadelphia, Pa: 2010.

11 Platelet and Fibrin aggregation video Fibrin Formation Animation

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13 When you are greeting somebody else how would you say hello? Good-bye Hola Adios

14 Emboli - detached, traveling intravascular mass at a site distant from its point of origin. Thrombi intravascular mass which is fastened at the point of origin. Proximal DVT - DVT that occurs in the veins of the thigh (femoral vein, deep femoral vein, common femoral vein, iliac veins, popliteal vein) Distal DVT - DVT that occurs in the veins of the calf (anterior tibial vein, posterior tibial vein, peroneal vein)

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16 Age annual incidence from 10 per 100,000 in adolescence and 1/100 in old age. History of VTE strongest known risk factor for recurrence, risk is highest during first 6 months after VTE Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

17 Major General Surgery Abdominal or thoracic operation requiring general anesthesia lasting > 30 minutes. Coronary artery bypass Surgery for gynecological malignancies Major urological surgery Nuerosurgery Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

18 Major Orthopedic Surgery Lower extremity orthopedic operations are high risk Without prophylaxis, ½ of the patients undergoing elective total hip or knee replacement develop VTE Only 5% manifest symptoms of VTE Arthroscopic knee surgery is low risk prophylaxis is optional. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

19 Spinal Cord Injury Overall incidence of DVT within 3 months of paralytic injury is 38% Development of PE is 5% Greatest risk is within first 2 weeks after injury Gradual atrophy of the leg muscles may cause individuals to develop small caliber collateral viens around old venous thrombi that completely obstruct the major deep leg veins. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

20 Multiple Trauma DVT in 47% of trauma patients, including proximal DVT in 12%. DVT found in 56% of patient with lower limb orthopedic or pelvic injury 40% of patients in whom primary site of injury was face, chest or abdomen had DVT as well Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

21 Malignancy VTE increases 2 to 3 fold in patients undergoing surgery for malignant disease vs nonmalignant surgeries Advanced cancers are associated with a high incidence of VTE High incidence in breast, lung, brain, pelvis, rectum, pancreas and GI tract. Chemo drugs increase risk Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

22 Myocardial Infarction MI is associated with DVT The VTE risk of pts hospitalized with acute MI is comparable to that of moderate-risk general surgery pts Similar associations age, bed rest and venous stasis. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

23 Congestive Heart or Respiratory Failure Medical Patients with Enoxaparin (MEDENOX) trial. 15% of pts Class III or IV had confirmed episode of VTE. Prevention of Cardiopulmonary Disease with Enoxaparin (PRINCE) study developed VTE Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

24 Prior VTE Previous episodes of VTE increase risk of reoccurrence, especially in high risk conditions In study, pts with h/o VTE were 8 times more likely to develop a new episode. Age Pt > 40 VTE is rare in children and young pts typically have strong predisposing factors such as multiple traumas, leg fractures, indwelling central venous lines Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

25 Immobility 15% of pts on bed rest for < 1weekhave risk of venous thrombosis The incidence rose to 80% in pts in bed longer than 1 week Hemiplegia 60% in paralyzed limbs of stroke pts compared with 7% in non paralyzed Prolonged immobility combined with other major risk factors increases the likelihood of VTE Economy class syndrome Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

26 Varicose Veins Weak risk factor. Decreases with age: odds ratios 4.2 at 45 years, 1.9 at 60 years and 0.9 at 75 years. VTE is reduced after surgical removal Obesity No association with excess weight. Morbid obesity risk alone is low. Pregnancy the absolute risk of VTE during pregnancy or postpardum is low Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

27 Pregnancy PE is a leading cause of maternal death after childbirth. 1 per 1000 births, 1 fatal PE per 100,000 births. The incidence of DVT was similar for pregnant and non pregnant women of similar age, but incidence was 20 times higher during postpartum period vs non-pregnant period. VTE in pregnancy is increased by smoking, prior VTE and inherited thrombophilias. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

28 Oral contraceptives HRT - have a 2-4 fold increased of icreased risk of venous thrombosis compared with women taking HRT. Women with h/o VTE using HRT are at greater rise. Men receiving estrogen for prostate cancer. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

29 Antiphospholipid Antibody Syndrome Rates of 6 to 8% in pts with lupus Those patients with antibody tithers above 95 th percentile have a 5.3-fold increased risk of developing DVT or PE over the next 5 year period. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

30 Antithrombin Deficiency pts are at the great risk for VTE than those with protein C and S deficiency. In a study up to 85% of pts with AT deficiency experienced a thromboembolic event by age 50. Protein C and S deficiencies APC Resistance Factor V Leiden Factor II high in whites of European descent. Coagulation Factors VIII, IX and XI have been linked with increased thrombotic risk. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

31 Hyperhomocysteinemia pts with elevated homocysteine are at an increased risk for recurrent VTE. Other Hereditary Risk Factors Blacks >Whites >East Asian Men > women Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

32 Hello How are you doing? Very well ok Hola, Como estas? Muy bien Asi-asi

33 Symptoms Leg swelling Pain Warmth Signs Superficial veins may be dilated Palpable cord Pain in back of knee Homan s sign Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

34 Laboratory test Serum concentration of D-dimer Diagnostic test Compression ultrasound is the most commonly used test to diagnose DVT. Venograghy Gold standard for DVT diagnosis. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

35 Symptoms Cough, chest pain, chest tightness, SOB, or palpitation. Hemoptysis If clot is massive dizziness or light headedness May be confused with MI Signs Tachypnea and tachycardia Diaphoresis Neck vein distended (possible) Massive PE cyanotic and hypotensive Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

36 Laboratory test D-dimer Computerized (CT) scan V/Q scan Pulmonary angiography I s the gold standard for diagnosing PE. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

37 Clinical Feature : pretest Probability of DVT Score Tenderness along entire deep vein system 1 Swelling of the entire leg 1 Greater than 3cm difference in calf circumference 1 Pitting edema 1 Collateral superficial veins 1 Active cancer 1 Prolonged immobility or paralysis 1 Recent surgery or major illness 1 Alternative diagnosis other than DVT -2

38 From: Disease Management CURRENT Practice Guidelines in Primary Care 2014, 2014 Legend: Date of download: 1/21/2015 Copyright 2015 McGraw-Hill Education. All rights reserved.

39 From: Disease Management CURRENT Practice Guidelines in Primary Care 2014, 2014 Legend: Date of download: 1/21/2015 Copyright 2015 McGraw-Hill Education. All rights reserved.

40 Clinical Feature: Pretest Probability of PE score Clinical evidence of DVT 3 Other Dx less likely than PE 3 Heart rate > Immobility > 3 day or major surgery within 4 weeks 1.5 Previous DVT/PE 1.5 Hemoptysis 1 Malignancy 1 Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

41 High 3 or greater (75% risk of DVT) Moderate 1 or 2 (20% risk of DVT) Low 0 (3% risk of DVT)

42 High 6 or greater (>70% risk of PE) Moderate 2 6 (20 30% risk of PE) Low less than 2 (2 3% risk of PE)

43 The acute phase of VTE (7 days) requires rapid anticoagulation to prevent thrombus extension and embolization. Early maintenance phase (7days to 3 months) is aimed to reduce the risk of long-term sequalae Holbrook A, Schulman S, Witt D, et al. Evidence based management of anticoagulant therapy: antithrombic therapy and prevention of thrombosis. Chest 2012; 141 (2 supp): e184s. Accessed may 2015

44 Acute DVT of leg or PE warfarin with LMWH Initiate warfarin and LMWH the same and continue LMWH of 5 days or until INR above 2 Treatment for 3 months Proximal DVT of leg or PE Tx for 3 months Unprovoked VTE Extended Tx recommended over 3 months Holbrook A, Schulman S, Witt D, et al. Evidence based management of anticoagulant therapy: antithrombic therapy and prevention of thrombosis. Chest 2012; 141 (2 supp): e184s. Accessed may 2015

45 Acute DVT/PE IVC filter with anticoagulants is not recommended PE specific PE with hypotension use thrombolytics PE without hypotension use thrombolytics Thrombolytic agent is used, short infusion time are suggested over prolonged infusion times. Upper extremity DVT Axillary or more proximal veins LMWH, UFH or SC UFH Holbrook A, Schulman S, Witt D, et al. Evidence based management of anticoagulant therapy: antithrombic therapy and prevention of thrombosis. Chest 2012; 141 (2 supp): e184s. Accessed may 2015

46 Compression stockings Intermittent pneumatic compression (IPC) IVC filters ambulation Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: a pathophysiologic approach 9e.USA: McGraw-Hill; accessed may 2015

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48 FDA Approvals Dabigatran Rivaroxaban Apixaban Edoxaban VTE prophylaxis No Yes Yes No VTE treatment Yes Yes Yes Yes

49 Pharmacokinetics Dabigatran Rivaroxaban Epixaban Edoxaban Target Thrombin FXa FXa FXa Peak effect (h) Half-life (h) Dosing Bid Qd Bid Qd Clearance 80% renal 20% biliary 66% renal 33% biliary 25% renal 75% biliary 50% renal 50% bile/ intestinal

50 Dabigatran Treatment: 150mg po bid after 5-10 days of parental anticoagulation. CrCl > 30ml/min Reduction of risk of recurrence: 150mg po bid after previous treatment. CrCl > 30ml/min. CrCl <30ml/min or on dialysis dosing recommendations cannot be provided. CrCl <50ml/min with concomitant us of P-gp inhibitors. Avoid concomitant use. Pradaxa [package insert].ridgefield,ct: Boehringer, Ingelheim Pharmaceutical Inc; 2015

51 Dabigatran Swallow capsule whole and take with full glass of water. If dose is not taken on time, take as soon as possible on same day or skip dose if it cannot be taken at least 6hrs before the next dose. DO NOT DOUBLE UP Pradaxa [package insert].ridgefield,ct: Boehringer, Ingelheim Pharmaceutical Inc; 2015

52 Dabigatran Converting from warfarin d/c warfarin and start pradaxa when INR <2 Converting to warfarin CrCl > 50, start warfarin 3 days before d/c dabigatran CrCl 30-50, start warfarin 2 days before d/c dabigatran CrCl 15-30, start warfarin 1 day before d/c dabigatran CrCl < 15 no recommendation can be made. Pradaxa [package insert].ridgefield,ct: Boehringer, Ingelheim Pharmaceutical Inc; 2015

53 Dabigatran Converting from parentals Start dabigatran 0-2 hrs before the time that the next parental drug was to have been administered or at the time parental is d/c Converting to parentals Wait 12 hrs (CrCl >30) or 24hrs (CrCl <30) after the last dose of dabigatran before initiating parental anticoagulant. Pradaxa [package insert].ridgefield,ct: Boehringer, Ingelheim Pharmaceutical Inc; 2015

54 Dabigatran Discontinuation for surgery d/c dabigatran 1-2 days (CrCl >50) or 3-5 days (CrCl <50) before surgery. Consider longer times for pt undergoing major surgery, spinal puncture, epidural catheter, or port Pradaxa [package insert].ridgefield,ct: Boehringer, Ingelheim Pharmaceutical Inc; 2015

55 Rivaxoban Treatment DVT/PE and reduction in recurrence: 15mg po bid with food for the first 21 days, then 20mg po d with food for the remaining. Prophylaxis of DVT following Hip or Knee surgery: 10mg po qd with or without food CrCl < 15 avoid use Hepatic impairment (Child-Pugh B and C) avoid use Avoid concomitant use with P-gp and strong CYP3A4 inhibitors Xarelto [package Insert]. Titusville, NJ: Jannsen Pharmaceuticals;2011

56 Rivoraxaban Food considerations 15mg and 20mg tablets should be taken with food while the 10mg can be take with or without food. Tablets may be crushed and mixed applesauce immediately prior to use. Stable is water or applesauce for up to 4 hrs Tablets can be given via NG tube or gastric feeding tube Xarelto [package Insert]. Titusville, NJ: Jannsen Pharmaceuticals;2011

57 Rivaroxaban Converting from warfarin d/c warfarin and start rivaroxaban when INR<3 Converting to warfarin No clinical trial data available. Recommended to d/c rivaroxaban and begin both a parental and warfarin at the time the next dose is do. Xarelto [package Insert]. Titusville, NJ: Jannsen Pharmaceuticals;2011

58 Rivaroxaban Converting to other other anticoagulants d/c rivaroxaban and give 1 st dose of other drug at time of next dose of rivaroxaban would have been taken. Converting from other anticoagulant Start 0-2 hrs prior to next scheduled evening administration of the drug and d/c the administration of the other anticoagulant. Xarelto [package Insert]. Titusville, NJ: Jannsen Pharmaceuticals;2011

59 Rivaroxaban Discontinuation for Surgery Stop 24hrs before procedure to reduce the risk of bleeding. Restart after surgery as soon as hemostasis has been established. Xarelto [package Insert]. Titusville, NJ: Jannsen Pharmaceuticals;2011

60 Apibaxan Treatment of DVT/PE: 10mg bid for 7 days followed by 5mg bid. Reduction in the risk of recurrent DVT and PE: 2.5mg po bid Prophylaxis of DVT after hip/knee replacement: 2.5mg bid Hepatic: no dose adjustments Renal: adjustment are not required for this indications Eliquis [package Insert]. Princeton, New Jersey: Bristol-Myers Squibb; 2014

61 Apixaban Administration considerations 5mg and 2.5mg may be crushed and suspended in 60ml D5W and immediately given through NG tube Eliquis [package Insert]. Princeton, New Jersey: Bristol-Myers Squibb; 2014

62 Apixaban Converting from warfarin d/c warfarin and start apixaban when INR<2 Converting to warfarin d/c apixaban and start warfarin and parental anticoagulant at the same time the next dose of apixaban would have been taken. d/c parental when INR > 2 Converting between apixaban and other anticoagulants. d/c one and begin taking at time of next scheduled.

63 Apixaban Surgery considerations Apixaban should be d/c at least 48 hrs prior to surgery with a moderate or high risk of unacceptable bleeding. Apixaban can be d/c at least 24hrs prior to low risk surgery. Bridging coagulation between during the 24-48hrs after stopping is not required. Restart after surgery. Eliquis [package Insert]. Princeton, New Jersey: Bristol-Myers Squibb; 2014

64 Edoxaban Treatment of DVT/PE: 60mg qd Not indicated for prophylaxis CrCl 15-50ml/min or body weight less than or equal 60kg or who use certain P-gp, recommended dose is 30mg qd Renal: not recommended in CrCl <15 Hepatic: not recommened in moderate to severe impairment (Child-Pugh B and C). No dose reduction needed in mild (A). Sayvasa [package Insert]. Tokyo, Japan: Daiichi Sankyo Company: 2015

65 Edoxaban Administration Considerations Take without regard to food If dose is missed take as soon as possible on the same day. Dosing should resume as normal the next day. Do not double up. Sayvasa [package Insert]. Tokyo, Japan: Daiichi Sankyo Company: 2015

66 Edoxaban Converting to Edoxaban From warfarin Other anticoagulants LMWH UFH Recommendation d/c warfarin and start edoxaban when INR<2.5 d/c current anticoagulant and start edoxaban at the next scheduled dose of other d/c LMWH and start Edoxaban at the time of next scheduled administration of LMWH d/c the infusion and start edoxaban 4 hours later Sayvasa [package Insert]. Tokyo, Japan: Daiichi Sankyo Company: 2015

67 Edoxaban Converting from Edoxaban From Recommendation edoxaban edoxaban edoxaban edoxaban If taking 60mg reduce to 30mg and begin warfarin. If taking 30mg reduce to 15mg and begin warfarin. d/c edoxaban once INR > 2 Parenteral option: d/c edoxaban and administer a parental anticoagulant and warfarin at the time of the next scheduled dose. Once INR > 2 d/c parental anticoagulant and continue warfarin D/c edoxaban and start the anticoagulant at the time of the next dose of edoxaban d/c edoxaban and start the parental anticoagulant at the time of the next dose of edoxaban

68 Surgery Discontinue edoxaban at least 24 hours before invasive or surgical procedure. Restart after the surgery as soon as adequate hemostasis has been established Pharmcodynamic effect time of onset is 1-2 hours. Administer a parental anticoagulant and then switch to edoxaban. Sayvasa [package Insert]. Tokyo, Japan: Daiichi Sankyo Company: 2015

69 How much? The bill Shirt, Shoes, dress Cuanto cuesta? La cuenta La camisa, los zapatos, el vestido

70 Pregnancy Commonly used for the treatment and prevention of DVT/PE UFH and LMWH are preferred because they do not cross the placenta. Warfarin is a category X Women of childbearing age taking warfarin should be on contraception. Dabigatran, rivaroxaban and apixaban should be avoided.

71 Pediatrics Primarily secondary to prematurity, cancer, trauma, surgery, congential heart disease and lupus. Typically develop DVT associated with indwelling catheters. Rarely develop idiopathic VTE. UFH and warfarin are the most widely used. LMWH is recommended due to low drug interaction profile and less frequency laboratory testing. Recommend anti-factor Xa levels between 0.5 and 1 unit/ml.

72 Cancer Therapy should continue for 3-6 months. Anticoagulation should continue for as long as the cancer is active and while the patient is receiving antitumor therapy The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend LMWH for these patients, but most continue to receive warfarin LMWH are expected to be an advantage in metastatic disease, treatment with aggressive chemotherapy, liver dysfunction, poor nutritional status

73 Risk Factors for Major Bleeding While Taking Anticoagulation Therapy Anticoagulation intensity Initiation of therapy (1 st few days and weeks) Unstable anticoagulation response Age >65 Concurrent antiplatelet therapy Concurrent NSAIDs use history of GI Bleeding

74 Risk Factors for Major Bleeding While Taking Anticoagulation Therapy Recent surgery or trauma High risk for fall/trauma Heavy alcohol use Renal failure Cerebrovascular disease Malignancy

75 Warfarin INR > 4.5 without evidence of bleeding may lower by withholding warfarin and adjusting warfarin. Vitamin K can be administered parentally or orally but oral rout e preferred. INR and no bleed routine use or vitamin K has not been shown to affect the risk of developing subsequent bleeding or thromboembolism vs withholding warfarin alone. INR > 10 without bleed suggest oral vitamin k 2.5mg

76 Fresh Frozen Plasma (FFP) Obtained from human blood and contains all the clotting factors found in plasma Dosing is based on pt weight. Each unit of FFP contains mls

77 Clotting Factor Concentrates Contain one or more clotting factors Four major types of products rfviia Three factor PCC which contains II,IX,X (inactivated) Four factor PCC which contains II,IX,X and VII (inactivated) Activated PCC contains VII (activated) and II,IX and X (inactivated)

78 Protamine Sulfate Combines with heparin to form an invactivated salt 1mg of protamine neutralizes 100 units of heparin (max of 50mg) Partially reversal LMWH There is no specific reversal for NOACs

79 Antidote neutralizing agents Aripazine Synthetic small molecule with broad activity against heparin, LMWH, and NOACs Andexanet Modified FXa direct reversal agent used against the FXA inhibitor medications Idarucizumab Humanized antibody frament directed against dabigatran

80 Any Questions?