Anticoagulation

Question 1

Warfarin

Answer 1

-Coumadin
-Inhibits factors VII, IX, X, II, proteins C and S
-Duration: 2- 5 days
-Reversal: fresh frozen plasma, vitamin K ((phytonadione), PCC (Kcentra), aPCC (FEIBA)

-Warfarin MOA:
-Inhibits VKORC (a protein that reduces Vitamin K to activate it)
-Inhibits creation of Vitamin K dependent factors: X, IX, VII, II (1972) and protein and C and S
-Contraindicated in pregnant patients
-Warfarin reversal agents and their times to onset
-Administer Vit K (6 hours)
-FFP (<1 hour)
-Prothrombin Concentrate Complex (immediate)

-Patient started on Coumadin and develops skin necrosis:
-Warfarin induced skin necrosis
-Seen in patients with protein C and S deficiency
-Short half-life of protein C and S (natural anticoagulants)= brief period hypercoagulable with initial inhibition of protein C & S
-Important to bridge with Lovenox when starting coumadin

Question 2

FFP

Answer 2

-Contains factors VII, IX, X, II (diluted), fibrinogen, proteins C and S
-Onset: 1-4 hours; duration of action: less than/ equal to 6 hours
-Large administration of volume (200 mL per unit)

FFP - All coag factors, protein C and S, ATIII and fibrinogen. Highest concentration of ATIII

-When to use FFP: any coagulation disorder including Antithrombin III deficiency

Question 3

Vitamin K (phytonadione)

Answer 3

-Cofactor for hepatic production of factors VII, IX, X, II
-Onset: 6-10 hours (PO;) 1-2 hours (IV)
-IV if major bleeding, or emergent procedure (≤6 hours)
-

Question 4

PCC (Kcentra®)

Answer 4

-Contains factors, including VII, IX, X, II (at a concentration 25x FFP)
-Onset: 5-15 minutes
-Duration of action: 6-8 hours
-Contains heparin – contraindicated in patients with HIT
-Contraindicated in disseminated intravascular coagulation (DIC) due to high risk of thrombosis

Question 5

aPCC (FEIBA®)

Answer 5

-Contains factors VIIa (activated), IX, X and II
-Onset: 15-30 minutes
-Duration of action: 8-12 hours
-Consider use in patients with HIT
-Higher thrombotic risk due to activated factor VII

Question 6

Heparin

Answer 6

-Binds antithrombin III (ATIII)
unfractionated heparin (UFH): Inhibits thrombin and some factor Xa
Enoxaparin (Lovenox): Inhibits factor Xa and thrombin
Reversal: protamine
Consider pre-medicating with corticosteroids and antihistamines in those with prior exposure to protamine or fish allergy (potential for anaphylactoid reactions)
Protamine can cause hypotension and bradycardia

Heparin – cleared by reticuloendothelial system (macrophages, spleen). SE = osteoporosis and alopecia
Lovenox vs heparin – Lovenox has lower bleeding risk, mortality, and recurrent DVT risk

-Determine effectiveness of Lovenox
-Check factor Xa levels
-Unlike heparin, Lovenox weakly reversed by protamine

Question 7

Dabigatran (Pradaxa)

Answer 7

Inhibits thrombin
Reversal: Idarucizumab (Praxbind- Binds to both thrombin-bound and free dabigatran with higher affinity than thrombin); PCC; Reversed with dialysis

Question 8

Direct Oral Anticoagulants

Answer 8

Direct Oral Anticoagulants: Apixaban (Eliquis), Betrixaban (Bevy), Edoxaban (Savaysa), Rivaroxaban (Xarelto)
Direct Oral Anticoagulants: Apixaban (Eliquis), Betrixaban (Bevyxxa), Edoxaban (Savaysa), Rivaroxaban (Xarelto)

Reversal: Andexanet alfa (Andexxa); PCC

andexanet alfa/ Andexxa= decoy- receptor for factor Xa inhibitor molecules

Question 9

Intravenous Direct Thrombin Inhibitors

Answer 9

Intravenous Direct Thrombin Inhibitors: Argatroban, Bivalirudin (Angiomax)
Inhibits thrombin
Reversal: FFP

Question 10

Thrombolytics

Answer 10

Alteplase (Activase®, Cathflo Activase®), Tenecteplase (TNKase®)
-Initiates fibrinolysis by binding to fibrin in a
thrombus, converting plasminogen to plasmin
-Reversal: Cryoprecipitate, Aminocaproic acid (Amicar- Binds competitively to plasminogen; blocking binding of plasminogen to fibrin and the subsequent conversion to plasmin, resulting in fibrinolysis

-MOA tPA:
-Activates plasminogen, breaks down fibrinogen
-Reverse= aminocaproic acid
-Contraindications:
-Absolute= active internal bleeding, recent CVA or neurosurgery, recent GI bleed, intracranial pathology
-Relative= surgery past 10 days, recent organ biopsies, recent delivery, recent major trauma, uncontrolled hypertension

Question 11

Antiplatelets

Answer 11

Bleeding associated with Plavix: Tx is platelets

Question 12

Uremia

Answer 12

Uremia inhibits release of vWB
Best acute (emergent) treatment for bleeding with uremia is DDAVP. HD takes too long, but used for all other cases

Uremic platelet dysfunction – first line is DDAVP. Cryo is 2nd. HD is 3rd

Platelet disorder will have what coagulation lab abnormality: increased bleeding time (PT and PTT not reliably affected)

Question 13

Direct thrombin inhibitors

Answer 13

Fondaparinux – direct thrombin inhibitor (factor IIa)
Argatroban = Administered IV, liver metabolism. Follow PTT
Bivalirudin = Administered IV, renal metabolism. Follow PTT
Dabigatran (Pradaxa) = oral, Idarucizumab is the reversal, Can also be dialyzed

Question 14

Direct Factor Xa inhibitors

Answer 14

Direct Factor Xa inhibitors – Hold 2-3 days before surgery
Rivaraxaban (Xarelto) – oral –. Avoid in patients with kidney disease, metabolized in kidney
- Reversal - Andexanet alfa or PCC
Apixaban (Eliquis). – oral – avoid this in patients with liver disease – hepatic clearance
- Reversal Andexanet alfa or PCC
Need to adjust for renal insufficiency. Less bleeding cx vs warfarin with above

Question 15

Continuation of Statin therapy

Answer 15

Continuation of Statin therapy perioperatively decreases all-cause mortality

Question 16

Insulin pre-operatively

Answer 16

Insulin pumps should be continued at sleep basal rates;
On the morning of surgery, take 50% of intermediate-acting (NPH) or long-acting insulin
Short-acting insulin should be held
Regular insulin is considered short acting and should be held

Question 17

TEG parameters

Answer 17

R value = Time elapsed until clotting begins = represents activation of clotting factors = if high, give FFP
- 5-10 minutes is normal
MA (maximum amplitude) – measures function of platelets and fibrin – represents maximum clot strength
- < 50 mm = transfuse platelets if the patient is actively bleeding. Can also give DDAVP
Alpha angle = speed of clot strengthening, estimates fibrinogen level
- < 45 degrees = deficiency in fibrinogen = Give Cryoprecipitate
LY30 (lysis at 30 minutes) – measure of fibrinolysis – normal is 0-3%
- > 3% = Give tranexamic acid
K time – Give cryo if high
- 1-3 minutes is normal

Question 18

Prothrombin complex

Answer 18

Facto V, X, calcium, platelet factor 3, prothrombin  forms on platelets catalyzes the formation of thrombin

Question 19

Thrombin

Answer 19

Thrombin (Factor II) = key to coagulation
Converts fibrinogen (factor I) to fibrin (factor Ia)
Activates V and VIII and platelets

Fibrin + platelets = platelet plug
Fibrin cross links platelets by binding GpIIb/IIIa

Question 20

Antithrombin III Key to anticoagulation

Answer 20

• Binds and inhibits thrombin (II)
• Inhibits factor II (thrombin), IX, X, XI
• Heparin activates AT-III

Question 21

Protein C

Answer 21

inhibits factor V and VIII, and degrades fibrinogen

Question 22

Activated Clotting Time

Answer 22

Want ACT 150-200 for full dose AC, >480 for cardiac bypass

*useful measure of anticoagulation during major cardiovascular surgery

Question 23

Cryoprecipitate

Answer 23

Cryoprecipitate – Has highest levels of vWF-VIII, fibrinogen
- Used in von-Willebrand’s and hemophilia A (VIII)

Question 24

Glanzmann’s thrombocytopenia

Answer 24

Glanzmann’s thrombocytopenia - GpIIb/IIIa receptor deficiency on platelets, prevents fibrin from linking platelets together
Prolonged bleeding time, normal PT, PTT
Fibrin usually binds the receptors together.
Dx: platelet function analyzer
Tx: Platelets

Question 25

Bernard Soulier

Answer 25

- GpIb receptor deficiency on platelets (Can’t bind to collagen). Prolonged bleeding time, normal PT, PTT Dx: platelet function analyzer Tx: platelets

Question 26

Hemophilia A

Answer 26

Hemophilia A – Give factor VIII (best) or cryo Hemarthrosis -> do no aspirate tx Give factor VIII Ice, Can get alloantibodies if given factorsIf patient has high inhibitory titers  give factor VII For major surgery Preop levels: 80 to 100 percent for hemophilia A, taper post op levels to 50% for 10-14 days -Factors missing in Hemophilia A: -Hemophilia A = Factor VIII, prolongation of PTT -Tx= factor VIII or cryo

Question 27

Hemophilia B

Answer 27

Hemophilia B – Give factor IX or FFP Hemarthrosis -> do no aspirate tx Give factor IX If patient has high inhibitory titers  give factor VII For major surgery Preop levels: 60 to 80 percent for hemophilia A, taper post op levels to 50% for 10-14 days -Factors missing in Hemophilia B: -Hemophilia B= Factor IX, prolongation of PTT -Tx= factor IX or FFP

Question 28

Von Willebrand’s disease

Answer 28

Von Willebrand’s disease MC congenital bleeding issue Epistaxis = MC sx PT normal, PTT can be normal or high Prolonged bleeding time (ristocetin test) = dx Type I (Autosomal Dominant) - MC 70% mild symptoms. Low level of vWF. #1 treatment for surgical prophylaxis = DDAVP. #1 treatment for acute bleeding recombinant VIII:vWF. Type II (Autosomal Dominant) - defect in vWF. Tx: Recombinant factor VIII:vWF, Some variants can be treated with Cryo or DDAVP Type III (Autosomal recessive) - Complete deficiency of vWF. most severe. Tx: Recombinant VIII:vWF,. DDAVP and cryo will not work for type III -Von Willebrand’s Disease -Type I: MC, reduced quantity of vWf, tx= desmopressin (for most patients) or cryoprecipitate -Type II: Dysfunctional vWF, tx= desmopressin or cryoprecipitate -Type III: Complete absence of vWF, desmopressin does not work, tx= cryoprecipitate or Factor VIII replacement

Question 29

Anti-thrombin III deficiency

Answer 29

Will have heparin resistance Tx: Recombinant ATIII or FFP (Has highest concentration of anti-thrombin III) then try heparin again. 2nd line is switch to direct thrombin inhibitor -Tx= ATIII concentrate or FFP, prior to heparin admin; then start on long-term anticoagulant

Question 30

Anti-phospholipid syndrome

Answer 30

Anti-phospholipid syndrome Thrombosis, venous AND arterial Anti-cardiolipin and lupus anticoagulant antibodies Cardiolipin is a mitochondrial phospholipid. Hypercoagulable AND elevated PTT (does not correct with FFP) Tx: heparin and warfarin -Antiphospholipid syndrome: -Hx: symptoms of Lupus, prior DVTs, recurrent pregnancy losses -Prolonged PTT but are hypercoaguable -Caused by antibodies to cardiolipin and lupus anticoagulant -Tx: heparin bridge to coumadin

Question 31

HIT

Answer 31

HIT - IgG ab to platelet factor 4. IgG binds to heparin after formation of heparin-platelet factor 4 complex - Patients develop a white clot - Arterial and venous clots - Dx: ELISA ab test (quickest to get) Highly sensitive, low specificity. If positive, then get serotonin release assay (send out) o If ELISA is positive, then start argatroban - Platelet transfusion is contraindicated - Tx: argatroban (Liver metabolism), bivalirudin (renal excretion), Lepirudin (renal excretion), or fondaparinux then warfarin -Patient on coumadin undergoes surgery and following surgery platelets drop >50%: -Concern for Heparin Induced Thrombocytopenia -Suspicion with 4Ts score (thrombocytopenia, timing, thrombosis, and other possible causes) -ELISA testing anti-platelet-factor-4 for initial screening -Serotonin release assay for confirmation -Stop heparin immediately with sufficient clinical suspicion -Start safe anticoagulation (argatroban= classic; bivalirudin or fondaparinux also options)

Question 32

Phlegmasia cerulea dolens

Answer 32

Phlegmasia cerulea dolens – blue leg. Can lead to gangrene of leg. Occurs with Ileofemoral DVT. - Tx: catheter directed thrombolytic. If threatened  open thrombectomy. - 50% of these people have CA somewhere Phlegmasia alba dolens – white leg, less severe

Question 33

Post thrombotic syndrome

Answer 33

Pain, cramping, swelling, sensation of heaviness, ulcers Prevent with catheter directed thrombolytics for early DVT Can affect patients up to 2 years after dx – chronic valvular disruption

Question 34

MCC of death after gastric bypass

Answer 34

PE

Question 35

CABG just had an MI

Answer 35

Don’t do CABG if the patient just had an MI. 15% mortality

Question 36

Bergman’s triad

Answer 36

Bergman’s triad – mental status change, petechia, dyspnea. - Fat emboli

Question 37

May-Thurner syndrome

Answer 37

May-Thurner syndrome Compression of left common iliac vein by right common iliac artery and sacrum Predisposes patients to thrombosis MC presentation  acute left iliofemoral DVT with left leg swelling Treatment is AC, thrombolytics and stent placement

Question 38

Preventing hypothermia in the OR

Answer 38

Best measure  increase temperature in the room and forced warm air (bair hugger)

Question 39

SCD

Answer 39

SCD – improves venous return but also promotes fibrinolysis (release of tPA) Left leg 2X more common for DVT left iliac vein compressed by right iliac artery = May-Thurner syndrome

Question 40

Bridging

Answer 40

Only need to bridge patients for elective surgery if CHADSVASC score is > 7 or CHADS score > 5 Prosthetic mitral valve has a much high risk of thrombosis vs prosthetic aortic valve (higher flow rate) Bridging is not needed for aortic valves!!

Question 41

Thrombotic thrombocytopenic purpura

Answer 41

-Moschcowitz syndrome -Deficiency or inhibition of ADAMTS13, which leaves large von Willebrand factor multimers to increase platelet adhesion and activate coagulation in arterioles and capillaries Sx: thrombocytopenic purpura, neurologic manifestations due to microvascular disease in the brain, kidney injury or hematuria due to microvascular disease in the kidney, hemolytic anemia due to destruction of red cells, and fever

Question 42

Coagulation factors not synthesized in liver

Answer 42

Factor VIII, desmopressin

Question 43

Factor with the shortest half-life

Answer 43

Factor VI

Question 44

Patient presents with DVT and strong family history of DVT. What heritable blood clotting disorders would be on your differential?

Answer 44

-Factor V Leiden -Prothrombin Gene Defect 20210 -Protein C and S Deficiency -Antithrombin 3 Deficiency -Hyperhomocystenemia

Question 45

Patients with hyperhomocysteinemia, how to treat this?

Answer 45

-Folic acid and B12

Question 46

PT/ PTT

Answer 46

-Coumadin= WEPT = Warfarin Extrinsic pathway PT -PTT = intrinsic pathway -Factors measured by PT/INR: -Measures external pathway: factors II, VII, IX, X (1972) -Best test for liver synthetic function -Goal INR of 2-3 generally in anticoagulated patients -Factors measured by PTT: all except VII -Goal of 60-90 in anticoagulated patients

Question 47

Timing of surgery

Answer 47

Percutaneous angioplasty – wait 2 weeks before surgery Bare metal stent – elective surgery delayed till 30 days DES – elective surgery delayed until 6 months

Question 48

Any patient undergoing major intra-abdominal/pelvic operation for cancer or inflammatory bowel disease

Answer 48

needs 4 weeks anticoagulation

Question 49

PE

Answer 49

S1Q3T3 pattern for PE on EKG. A large S wave in lead I, a Q wave in lead III and an inverted T wave in lead III together indicate acute right heart strain Massive PE – hypotension! - If low risk of bleed Treat with SYSTEMIC tPA - If high risk of bleed (intracranial hemorrhage, s/p trauma/surgery)  catheter directed tPA -MC VS change: tachycardia, tachypnea -Respiratory alkalosis -MC EKG finding: sinus tachycardia -Classic S1Q3T3 finding is uncommon: classically associated with right ventricular strain due to pulmonary embolism. Characterized by a deep S wave in lead I, a pathological Q wave in lead III, and an inverted T wave in lead III. -New Right bundle branch block -Dx: -CT Pulmonary Arteriogram= study of choice -D-Dimer: sensitive- good for ruling out PE; high false positive rate -Tx= -Anticoagulation: Heparin bolus followed by drip for goal PTT 60-90 -Indications for thrombolytics: hemodynamic instability, right heart strain on echocardiogram -Pulmonary embolectomy (Trendelenburg Procedure): uncommon, surgical option if contraindication for thombolytics

Question 50

AC after PE or DVT

Answer 50

In patients requiring anticoagulation for treatment of DVT or pulmonary embolism and no history of cancer:  3 months anticoagulant therapy is recommended with dabigatran, rivaroxaban, apixaban over WARFARIN!!! Provoked DVT/PE – Usually stop at 3 months Unprovoked distal DVT – Usually stop at 3 months Unprovoked PE or unprovoked proximal DVT  LIFE LONG AC Recurrent VTE  lifelong AC Any CA history and VTE  lovenox or direct oral anticoagulation. LIFELONG unless malignancy resolved.

Question 51

IVC filter

Answer 51

PE with IVC filter placed – comes from ovarian (Gonadal) veins, superior to IVC, or UE Placement of IVC filters increases risk of DVT, IVC thrombosis, IVC perforation, can erode into duodenum or aorta IVC filter perforated into duodenum  Ex lap, duodenal repair, IVC filter removal and IVC repair IVCF filter indications - DVT and low cardiopulmonary reserve (severe pulm HTN,RHF) - Large, unstable, free floating IVC clot

Question 52

Homocystinuria

Answer 52

Homocystinuria – Inherited condition – autosomal recessive Causes thrombosis in ARTERIES Toxic metabolites to brain  seizures Skeletal abnormalities  interferes with collagen cross linking Tx: Pyridoxine vitamin B6, folate, B12

Question 53

Superficial vein thrombosis

Answer 53

Superficial vein thrombosis – if low risk (< 5 cm length, away from deep vein system)  NSAIDS and compression stockings If high risk >5 cm length, near deep vein system  needs AC

Question 54

Distal DVT below the knee treatment

Answer 54

(2 options): Need to do 1 because it can extend into larger veins - Anti-coagulate - Repeat US surveillance

Question 55

DVT associated with a central line

Answer 55

If you find a DVT associated with a central line, and still need the line, the recommendation is to start AC, and remove the line in 5 days to avoid embolus

Question 56

Frailty index

Answer 56

In patients over 65, the likelihood of developing periop complications is best measured by frailty index

Question 57

Thromboxane TXA2 (COX-1)

Answer 57

Secreted by platelets Increases platelets aggregation and promotes vasoconstriction Trigger release of Ca in platelets → exposes GpIb and GpIIb/IIIa receptors and causes platelet to platelet binding. ASA irreversibly binds cyclooxygenase, decreasing TXA production for the life of the platelet (platelets don’t have nuclear material) – results in decreased TXA production and decreased platelet aggregation

Question 58

Prostacyclin PGI2 (COX-2)

Answer 58

Secreted from the endothelium. Decreases platelet aggregation, promotes vasodilation, causes bronchodiliation Increases cAMP in platelets ASA irreversibly binds cyclooxygenase, but cyclooxygenase is re-synthesized in endothelium (has nuclear membrane unlike platelets) – results in normal PGI production and platelet inhibition

Question 59

Omentum

Answer 59

Has a dense amount of tissue factor used as hemostatic agent

Question 60

Blood transfusions

Answer 60

Stored PRBC lasts 3 weeks Type and screen – Looks for preformed abs to minor HLA antigens. Type and crossmatch – same as above but holds units MCC of mortality from transfusion is TRALI Blood is tested for Hep B, Hep C, HIV, West Nile, HTLV MC contaminant in transfusions- staph epidermidis MC contaminant in platelets  staph epidermidis Platelets (stored at room temperature) are MC product to have contamination Platelets lasts for 5 days stored All blood products have risk of transmitting HIV and hepatitis C EXCEPT albumin and immunoglobulins

Question 61

CMV negative prbc

Answer 61

CMV negative prbc – given to 1. CMV sero-negative pregnant mothers 2. Organ/bone marrow transplant donor/recipient 3. HIV 4. Low birth weight infants

Question 62

Platelet transfusion indications

Answer 62

Platelet transfusion indications – one 6 pack of platelets = 1 unit = should raise platelets by 50,000 - <10,000 (has high risk for spontaneous bleeding)) - <20,000 with infection or bleeding risk (post op patients) - <50,000 only with active bleeding or pre-procedure - Contraindication for transfusion of platelets: TTP, HUS, HELLP, HITT

Question 63

Platelet transfusion indications

Answer 63

-One 6 pack of platelets = 1 unit = should raise platelets by 50,000 - <10,000 (has high risk for spontaneous bleeding)) - <20,000 with infection or bleeding risk (post op patients) - <50,000 only with active bleeding or pre-procedure - Contraindication for transfusion of platelets: TTP, HUS, HELLP, HITT

Question 64

Acute hemolytic transfusion reaction

Answer 64

Acute hemolytic transfusion reaction – 2/2 to ABO incompatibility - Preformed recipient abs against donor RBC ABO antigens - Type II hypersensitivity reaction. Hemolysis. - Chills, fevers, Hypotensive, DIC, these patients are really sick - Will see RED URINE (hemoglobinuria) - Hemolytic anemia - Dx: low haptoglobin (<50), high free hgb, high Unc-bili, high LDH - Tx: fluids and pressors

Question 65

Febrile (nonhemolytic) transfusion reaction

Answer 65

Febrile (nonhemolytic) transfusion reaction = MC transfusion reaction - Sx: FEBRILE is the key to the presentation!!!!, But NO hemolysis - Cytokines released from DONOR WBC - MC occurs with platelets!! - Tx: WBC/platelet filter for future transfusion

Question 66

Urticaria

Answer 66

Urticaria – OR JUST ANY RASH (at IV site) - From recipient antibodies to donor plasma proteins - MCC is IgA deficient patient with preformed IgE antibodies to IgA - Tx: 1st slow the transfusion rate, 2nd Histamine blockers, supportive

Question 67

TRALI

Answer 67

Transfusion-related acute lung injury Donor abs binds to recipients WBC then lodge in lung -acute, noncardiogenic pulmonary edema associated with hypoxia that occurs during or after a transfusion