Presentation on theme: "Introduction to thrombosis"— Presentation transcript:
1 Introduction to thrombosis Assistant Professor of MedicineHematology/Oncology2014
2 Objectives 1. Arterial Thrombosis: -Pathophysiology, Risk factors, Symptoms and Signs, treatment2. Venous Thrombosis:-Pathophysiology, Risk Factors, Symptoms and Signs3. Common anticoagulants4. Hereditary and acquired Hypercoagulable Disorders
3 Summary of Hemostasis Extension of clot Stabilization by limited by: fibrin formation(clotting cascade)Natural anticoagulantsPlatelet plugformsFibrinolysis
4 Arteries versus Veins Thick, muscular Thin, pliable High pressure High oxygenThin, pliableLow pressureLow oxygenException: pulmonary artery –O2 low
5 Blood Clotting Arterial Venous Plateletsmore importantBlood clotting factorsmore important
6 PathogenesisAtherosclerosis is a slow process that starts in childhood and results in occlusion of arterial blood vesselsInterruption of blood flow leads to hypoxia which causes ischemic damage of tissue, in the worst case tissue death (infarct)Ischemia causes pain and malfunction of tissue/organ ( angina/Myocardial infarct, arrhythmias in the heart)
7 Risk factors for arterial thrombosis SmokingHTNcholesteroldiabetesHomocysteine ?obesitysedentary life styleAdvanced ageFamily HistoryInflammationEndothelial dysfunctionFatty streakSoft plaqueHard plaquePlaque ruptureThrombosis/Occlusion
8 Arterial Thrombosis-Clinical manifestations 1. Myocardial Infarction (Heart Attack)-chest/arm pain pain, SOB, collapse, stomach pain2. Cerebrovascular accident CVA (Stroke)-dizziness, slurred speech, facial droop, one sided arm/leg weakness3. Peripheral Vascular Disease (PVD), chronic versus acute-sudden onset of severe pain,palor, cold skin ( No pulse palpable)
9 Treatment of arterial thrombosis Acute: Anticoagulation with heparin plus thrombolytic (tPA, urokinase, streptokinase)=“clot busters”Long-term for primary or secondary prevention: antiplatelet therapy with ASA( acetylic salicylic acid=aspirin)After Stent placement: Clopidogrel (Plavix) and ASANo role for warfarinRisk factor modification important
10 Objectives 1. Arterial Thrombosis: -Pathophysiology, Risk factors, Symptoms and Signs, treatment2. Venous Thrombosis:-Pathophysiology, Risk Factors, Symptoms and Signs3. Common anticoagulants4. Hereditary and acquired Hypercoagulable Disorders
11 Case #1 24 y/o female AF cadet notices DOE over the course of 1 month Can’t finish 2 hour hiking exercise, sent to local EDCT Chest with PE protocol shows:
13 Case #2A 63 y/o male develops new Right sided bulky Lymph adenopathy, night sweats and weight loss.He is diagnosed with Diffuse large B-cell lymphoma and will require ChemotherapyHe undergoes placement of a PICC line R arm3 days later he returns with a swollen, painful Right arm that is warm and has a slightly dusky discoloration.US Doppler shows a thrombus in the axillary vein
14 Case #3A 76 y/o woman presents to the ER with a 2 day history of LE swelling. She also feels slightly SOB and has had hemoptysis on one occasion this morning.2 weeks ago, she underwent Right hip replacement. She finished a course of prophylactic heparin injections 4 days agoUS Doppler shows acute DVT extending from her popliteal vein into her femoral vein covering the entire thighCT Chest by PE protocol shows PE in the RLL with signs of early infarction.
15 Venous Thromboembolism (VTE) Incidence and Impact in the United StatesApproximately 2 million VTEs occur every year1Each year 1 person in 1,000 will experience his/her first VTE in the US2One third manifest pulmonary embolism ([PE], with or without deep vein thrombosis [DVT])Death within 1 month of diagnosis2:~6% of DVT cases~12% of PE casesRecurrent DVT:~17% of DVT patients 2 years after initial treatment*3~30% of DVT patients 8 to 10 years after initial treatment*†3,4*High dose standard heparin or LMWH for at least 10 days; oral anticoagulant therapy was initiated during the first week and continued for at least 3 months; †Unfractionated heparin was given as an initial IV bolus followed by IV infusion; oral anticoagulant therapy was initiated after the first week and continued for at least 6 months.1. Hirsh J, Hoak J. Circulation. 1996;93:2. American Heart Association. Heart Disease and Stroke Statistics – 2004 Update.3. Prandoni P et al. Haematologica. 1997;82:4. Pengo V et al. N Engl J Med. 2004;350:
16 NBC News Correspondent David Bloom. While covering the war in Iraq, Bloom was stricken with a fatal pulmonary embolism (PE), acomplication of DVT.“ March 2, 2011 Serena Williams suffers pulmonary embolism Tennis star undergoes emergency treatment in L.A. for complications stemming from blood clot in lungs”
17 Venous thrombosis-Clinical Manifestations 1. Extremities, Deep venous thrombosis (DVT)Swelling, Redness/dusky color, warmthsudden onset vs. gradual2. Pulmonary embolism (PE)SOB, acute versus gradualDiminished exercise capacitychest painsyncopecardiac arrest/deathLess common sites: Portal vein, renal vein,cerebral sinus vein
18 PE: Clinical Presentation Most Common Sx/Si Among 2454 Pts in International Cooperative Pulmonary Embolism RegistrySymptom or SignPercentDyspnea82Respiratory Rate >20/min60Heart Rate >100 beats/min40Chest pain49Cough20Syncope14Hemoptysis7Goldhaber SZ, et al. Lancet 1999.Goldhaber SZ, et al. Lancet 1999.
19 Venous thrombosis-Limb Sudden or gradual occlusion of a vein leads to-impaired venous return with blood flow “backing up”, edema develops due to increased hydrostatic pressure, pain present-blood flow through alternative routes leads to dilated superficial veins-thrombus leads to inflammatory response with redness and warmth of the affected area
20 Venous thrombosis-Pulmonary embolism Part of the thrombus can break off and travel through major veins, right heart into pulmonary artery until it becomes lodgedBlood flow through pulmonary artery is impaired by thrombus, Lung tissue past thrombus cannot participate in gas exchange, tissue can infarct (Pulmonary infarct)Increased pulmonary vascular resistance can lead to right ventricular dysfunctionIncreased airway resistance d/t bronchoconstrictionDecreased pulmonary complianceIf clot burden is high ( saddle embolus-both PA affected): cardiovascular arrest and death
22 Risk Factors for Venous Thrombosis Common:TraumaPost-surgeryImmobility/InactivityObesityPregnancyEstrogens/Birth controlMalignancyAgePrevious history of DVT/PE
23 Age and VENOUS THROMBOSIS 40 y.o.75 y.o.1:100RISK OF THROMBOSIS1:10001:10,0001:100,000AGE
24 Risk Factors for Venous Thrombosis Inherited procoagulant disorders-Factor V Leiden-Prothrombin gene mutation-Protein C deficiency-Protein S deficiency-Antithrombin deficiencyAcquired hypercoagulable states-clotting factors ( increased factors VII, VIII, XI)-systemic disorders( PNH, Myeloproliferative disorders, Malignancy, Vasculitic/proinflammatory disorders, Antiphospholipid syndrome)-Disseminated intravascular coagulation ( DIC)-Heparin-induced thrombocytopenia and thrombosis syndrome
25 Diagnosis of venous thrombosis SymptomsBlood work-elevated D-Dimer-Negative D-Dimer rules out thrombosisImaging for Limb:-Compression ultrasonography +/-US-Doppler,Imaging for Lungs:-CT scan-VQ scan
26 Hypercoagulable States DefectIncidence in PopulationPercent of Patients with Procoagulant StatesFactor V Leiden5-10%20-60%Prothrombin Gene Mutation2-4%6-8%Homocysteinemia--10%Protein C Deficiency1:200<5%Protein S DeficiencyAntithrombin Deficiency1:2-5,000<1%DysfibrinogenemiaNot known~1-2%Known Malignancy16-18%
27 Treatment of acute DVT/PE Treatment for acute clot is heparinHeparin inactivates activated clotting factors (clotting cascade initiated)Minimum time: 5 days and until warfarin is fully therapeutic-overlap heparin with therapeutic INR x 2 daysWarfarin used to prevent additional clotsWarfarin does not treat the acute clot-do not give alone for acute event!Reduction of vitamin K dependent factors takes at least 4-5 days regardless of INR
28 If we cannot anticoagulate Does not address the underlying hypercoagulable statePreference for removable devices, great for short term protection of patient (bleeding, surgery etc)Long-term: increases the risk of DVT
29 Bates, S. M. et al. N Engl J Med 2004;351:268-277
30 Objectives 1. Arterial Thrombosis: -Pathophysiology, Risk factors, Symptoms and Signs, treatment2. Venous Thrombosis:-Pathophysiology, Risk Factors, Symptoms and Signs3. Common anticoagulants4. Hereditary and acquired Hypercoagulable Disorders
35 Mechanism of Action - LMWH 5-sugarsequenceFactor XaLMWHAntithrombinFactor Xai
36 Warfarin Interferes with carboxylation of vitamin K dependent factors Factor II (thrombin), VII, IX, X,protein C, protein SProthrombin Time (PT)/INR is used to monitor warfarin because half life of Factor VII is the shortest (5-7 hours)
37 Warfarin Mechanism of Action Vitamin KAntagonismofVitamin KVIISynthesis of Non Functional Coagulation FactorsAlso affects Protein C and protein SIXXWarfarin acts as an anticoagulant by blocking the ability of Vitamin K to carboxylate the Vitamin K dependent clotting factors, thereby reducing their coagulant activity.IIWarfarin
38 Effect of Warfarin on Factor Activity Therapeutic INR once ALL factors suppressed
39 Mechanisms of Anticoagulation1 Intrinsic system(surface contact)Extrinsic system(tissue damage)XIIXIIaTissue factorXIXIaIXIXaVIIaVIIVIIIVIIIaXaFactor Xa inhibitors4,5Direct thrombin inhibitors4,5Vitamin K antagonists4Heparins2,3XXaThe efficacy/safety ratio for currently available therapies is less than satisfactory due to their ill-defined, multi-targeted activity. New antithrombotic strategies are needed that offer an improved efficacy/safety profile compared with existing antithrombotic agents.1,2Currently available antithrombotic agents include the heparins (UFH and Lovenox), vitamin K antagonists (warfarin), and direct thrombin inhibitors (hirudins).3–6The most widely used agents, heparins and vitamin K antagonists, have a range of actions on various components of the coagulation cascade. This contributes to the unpredictable clinical responses associated with these agents.3–5Other limitations of currently available antithrombotics include3–7High incidence of serious adverse effects, particularly bleeding complicationsRoutine monitoring of coagulation markers may be needed and represents a substantial burden in terms of time and costsNarrow therapeutic marginLimited effectiveness in preventing VTEFactor Xa inhibitors are a novel class of antithrombotic agents designed to selectively target only 1 core step in the coagulation cascade, leading to potent and targeted effectiveness.8VVaIIaIIIIa(Thrombin)FibrinogenFibrin1. Adapted with permission from Petitou M et al. Nature. 1991;350(suppl):30-33;2. Hirsh J, Fuster V. Circulation. 1994;89:3. Hirsh J et al. Chest. 2001;119(1 suppl):64S-94S.4. Nutescu EA, et al. Pharmacotherapy. 2004;24(7 Pt 2):82S-87S.5. Weitz JI, Hirsh J. Chest. 2001;119(1 suppl):95S-107S.
40 INR – Oral (warfarin) anticoagulation Therapeutic Range INR(Most situations)Mechanical Heart Valve INRDose:Diet (Vitamin K)MetabolismConcurrent medications**The higher the INR the higher the bleeding risk
42 Management of excessive anticoagulation Depends on INR level and presence of bleeding symptomsOptions:Hold warfarin dose until INR is in therapeutic rangeGive Vitamin K (po, im, iv), if patient not bleeding-takes hoursGive FFP iv (contains all clotting factors), results in partial or total reversal-used before urgent/emergent procedures-used for severe or life threatening bleeding-works immediatelyRecombinant Factor VII if all else fails ( caution: thrombogenic!)
44 New anticoagulants-No monitoring Dabigatran (Pradaxa): oral direct thrombin inhibitorFDA approved in US for Atrial fibrillation, 150 mg po bidslightly less bleeding risk than warfarinRivaroxaban (Xarelto): oral Factor Xa inhibitorFDA approved for A fib ( 20 mg qd) and DVT/PE treatment, 15 mg bid x 3 weeks, then 20 mg qdApixaban (Eliquis): oral Factor Xa inhibitor5 mg po bid for non-valcular A fibIncreased risk of stroke after stopping drug (Rebound)
45 Bridging case 45 y/o female PMH: HTN ‘idiopathic’ DVT in 2005, PE in 2/ days after leg injury.Antiphospholipid-Antibody syndrome (APLS)=severe hypercoagulable disorderChronic warfarin therapy (since 2/08) without complications
46 Oh by the way…Scheduled for FME in 7 days and was instructed to stop warfarin tomorrow.
47 BridgingUse of parenteral anticoagulants during period of withholding warfarin therapye.g. colonoscopy, surgery, multiple dental extractionParenteral anticoagulants: heparin, low molecular weight heparin (LMWH),Minimize period of time without anticoagulation
48 Typical bridging protocol 5 days before procedure-stop warfarin (pm dose)3 days before procedure start LMWH ( am injection)No LMWH on morning of procedureRestart LMWH within hrs after procedureStart warfarin on the evening of procedure: remember that is takes several days before warfarin is at therapeutic levelsFollow INR and stop LWMH once INR is at targetAnticoagulation clinics/PCP
49 What’s this patient’s risk of having thrombotic event off anticoagulation? LowModerateHigh
50 Managing patients on anticoagulation requiring invasive procedures Low risk: no recent (>12 months) venous thromboembolism, atrial fibrillation without h/o stroke or other risk factors or bileaflet mechanical cardiac valve in aortic positionPLAN:- stop warfarin 4-5 days before surgery, allow INR to return to normal. Use postoperative prophylaxis and simultaneously begin warfarin
51 Intermediate risk of thromboembolism Mechanical Heart ValveBileaflet (St. Jude) aortic valve and one:A.fib, prior CVA/TIA, DM, HTN, HF, age >75Atrial FibrillationCHADS-2 score of 3 or 4VTE within past 3 to 12 moNon-severe thrombophilia (i.e. heterozygous Factor V Leiden)PLAN:Stop warfarin 4-5 days before surgery, allow INR to return to normal, cover the patient beginning 2 d preoperatively with low dose UFH or prophylactic dose LMWH and then start therapy with LMWH and warfarin postoperatively vs. higher dose UFH or full dose LMWHCHADS-2: CHF, HTN, age >75, DM, prior TIA/CVA
52 Managing patients on anticoagulation requiring invasive procedures High risk: recent (<3 months) history of venous thromboembolism, Severe thrombophilia (APLAS, protein C or S def, multiple), mechanical cardiac valve in mitral position and old model of cardiac valve (Ball/cage), Atrial Fibrillation with CHADS-2 score of 5 or 6. Recent (3 mo) CVA/TIA, Rheumatic valve diseasePLAN:-stop warfarin 4-5 days before surgery, allow INR to return to normal-begin therapy with FULL dose of UFH or LMWH as the INR falls ( about 2 days preop)-UFH as sc. Injection, then IV drip in hospital-dc drip about 5 hrs before surgery-stop LMWH hrs before surgery
53 Managing patients on anticoagulation requiring invasive procedures-alternative option Low risk of bleedingContinue warfarin at lower dose and operate at an INR ofIntensity has been shown in RCT to be safe in gynecologic and orthopedic surgery patientsDose of warfarin can be lowered 4-5 days preopWarfarin therapy can be restarted at regular doses postoperatively, supplemented with low dose UFH or prophylactic LMWWH
54 Anticoagulants for Bridging Therapeutic dose (DVT/PE treatment dose)enoxaparin (Lovenox)1 mg/kg SQ bid or 1.5 mg/kg/daydalteparin (Fragmin)200 IU/kg/day or 100 IU/kg/bidUnfractionated heparin with therapeutic APTT (61-84 sec)Low doseenoxaparin 30 mg SQ twice daily or 40 mg SQ once dailydalteparin 2500 or 5000 units SQ once daily
55 Bridging Plan - LMWHStop warfarin approximately 5 days prior to procedure (Grade 1B)Initiate LMWH once INR below therapeutic levelUsually day 4 or 3 priorLast dose of LMWH 24 hr before surgery (grade 1C)Administer approximately ½ total daily dose instead of 100% (grade 1C)Resume LMWH approximately 24 hours after procedure when there is adequate hemostasis (grade 1C)Resume warfarin approximately 12 – 24 hrs after surgery (grade 1C)
56 Oral Anticoagulation and Dental Surgery “Although there is a theoretical risk of hemorrhage after dental surgery, the risk is minimal, and the risk may be greatly outweighed by the risk of thromboembolism.”1Grade 1B recommendation: continue warfarin around time of minor dental procedure (single or multiple tooth extraction and root canal procedure)2Arch Intern Med 1998;158: Chest 2008;133:299S
57 Objectives 1. Arterial Thrombosis: -Pathophysiology, Risk factors, Symptoms and Signs, treatment2. Venous Thrombosis:-Pathophysiology, Risk Factors, Symptoms and Signs3. Common anticoagulants4. Hereditary and acquired hypercoagulable Disorders
58 Indications of a congenital Defect in a patient with thrombosis First thrombosis age <50Family history of thrombosisRecurrent episodes of thrombosisThrombosis at unusual sitesNeonatal thrombosisThrombosis without apparent antecedent thrombogenic event
59 What are the (known) inherited Hypercoagulable States? 1. Factor V Leiden-Factor Va becomes resistant to activated Protein C (APC resistance)2. Prothrombin gene mutation (Factor II)Mildly elevated plasma levels of Factor II3. Deficiencies of Antithrombin III (AT III), Protein S and Protein C-Reduced amounts of natural anticoagulants leads to imbalance in the clotting cascade
61 Case #2 Issues: Long-term management Pregnancy Surgeries 19 y/o healthy and active woman is evaluated for swollen RLE x 5 days in local ERStarted on birth control 5 mo priorUS shows Right popliteal DVT“Hypercoag panel” drawn at time of presentation:Heterozygous for Factor V LeidenIssues:Long-term managementPregnancySurgeriesGenetic counseling (siblings, children)
62 Factor V LeidenAutosomal dominant genetic mutation (1994 in the Dutch city of Leiden)This is not a deficiency! but a structural change in the Factor VDiagnosis by DNA analysis ( heterozygotes vs homozygotes)
63 Mechanism of Factor V Leiden 1. Increased coagulation:-Factor V Leiden is inactivated more slowly by activated protein C than normal factor V-More Factor Va is available within the coagulation cascade, thereby leading to more thrombin generation2. Decreased anticoagulation:-Normal factor V, cleaved at position 506, is a cofactor together with protein S for protein C. Protein C cleaves factor VIIIa and factor Va-Lack of normally cleaved Factor V decreases the anticoagulant property of protein C (APC resistance)
64 Factor V Leiden Mechanism TF+ VIIaIX+VIIIX+V (=abnormal)IIFibrinolysis CLOTDegradation of Factors V, VIIIProtein C andProtein SAntithrombin
66 Prothrombin gene mutation PG20120A (Factor II mutation) genetic polymorphism that causes increased amount of prothrombin (factor II) in the circulationoccurs in ~2-3% of Caucasian population in the U.S.associated with VENOUS thrombosisat least half of clotting events precipitated by some stimulusmost people with the mutation DON’T clot
67 Testing for prothrombin gene mutation DNA analysis for prothrombin G20210A mutationDistinguishes heterozygotes and homozygotes
69 Deficiencies of natural anticoagulants Leads to imbalance between coagulation and anticoagulationNatural anticoagulants: Protein C,S and Antithrombin deficiencyPatients present early in life, usually with venous thrombosisOften additional risk factors are present
70 Natural Anticoagulants: AT III, protein C, S TFPI TF+ VIIaIX+VIIIX+VIIFibrinolysis CLOTDegradation of Factors V, VIIIProtein C andProtein SAntithrombinProtein C/S deficiencyHeparin
71 Asymptomatic carriers Thrombosis is a multi-risk disorderAdditional risk factors are often required to cross the thrombosis thresholdSome carriers will never have a thrombotic eventAsymptomatic family members rarely need anticoagulationProphylaxis during high risk events: pregnancy, surgery or immobilizationEstrogen therapy ( OCP, perimenopausal) is contraindicated-use anticoagulation
72 Acquired hypercoagulable States MalignancyPresence of a central venous catheterSurgery, especially orthopedicTraumaPregnancyOral contraceptivesHormone replacement therapy or Tamoxifen,Anti-angiogenesis (Bevacizumab, Thalidomide,Lenalidomide)Congestive heart failureAntiphospholipid antibody syndromeMyeloproliferative disorders (Polycythemia vera, Essential thrombocythemia)Paroxysmal nocturnal hemoglobinuria (PNH)Inflammatory bowel diseaseNephrotic syndromeHyperviscosity (Waldenstrom's macroglobulinemia, Multiple myeloma)Marked leukocytosis in acute leukemiaSickle cell anemiaHIV/AIDS
73 Antiphospholipid Antibody Syndrome Acquired hypercoagulable statePresence of antibodies that cause clotting (anticardiolipin AB, Lupus anticoagulant, beta2-glycoprotein1-AB) plus clinical event ( arterial or venous thrombosis)Very high risk of recurrence after initial event (10%/year, cumulative)Life-long anticoagulation recommendedNeed to “bridge” before procedures
74 Case #340 y/o female presents with idiopathic DVT LLE/PE at the age of 35Treatment with heparin/ warfarin x 6 monthsDoes well until 2 years later when she presents with recurrent PE, anticoagulation restarted7 months later she has a 3rd PE while therapeutic on warfarin (INR at 2.5), Filter placed, O2 dependentHypercoagulable panel shows very high titers for Antiphospholipid antibodiesGoal INR is raised to 3-46 months later, she develops DVT in RLE while on warfarin, gets transitioned to twice daily LMWH injections
75 Cancer is a hypercoagulable state 5-10% of patients presenting with idiopathic VTE will be diagnosed with cancer in the next months 1VTE has been found in 20-50% of cancer patients at autopsy 2Cancer patients have higher rates of recurrent VTE and bleeding than patients without cancer3,4,5Cancer patients with VTE have higher mortality than those without VTE 61 J Thromb and Haemost 2004;2: Am J Med Sciences 1938; 34: JCO 2000;18: Medicine 1999;78: Blood 2002; 100: NEJM 2000; 343: 1846
76 Thrombosis and Cancer DVT/PE most common Any location possible Recommendation: preferred is LMWH sc daily/bid as long as cancer not in remission due to high risk of recurrenceAlternative: warfarinNeed bridging if on warfarin.
78 Assistant Professor of Medicine Dental case studiesAssistant Professor of MedicineHematology/Oncology
79 Case 8A 66 y/o male with atrial fibrillation and no prior stroke, otherwise healthy, comes in for dental extraction. You shouldA) stop coumadin 4-5 days beforeB) lower his dose for 4-5 days to achieve an INR of and proceed with extractionC) Bridge the patient with LMWH after he stops coumadin 4-5 days beforeD) Bridge the patient with UFH after he stops coumadin 4-5 days before
80 Case 9A 55 y/o male with h/o unprovoked PE 2 months prior comes in for elective dental work (implants). How should you manage his anticoagulation?A) Proceed with dental implants and stop coumadin 5 days before and for 7 days post-op.B) Bridge the patient before , then hold anticoagulation post-op for 1 weekC) Postpone implantsD) Stop Coumadin, place temporary filter and proceed with implants. Have his PCP restart anticoagulation.
81 Case 1075 y/o patient undergoes dental extraction. He is on chronic coumadin for atrial fibrillation and restarts after his extraction. 1 week after extraction, he calls you with c/o fever and facial swelling. He reports pus from the socket. You see him in the office and diagnose him with a post-procedural infection. On exam, he is hypotensive and tachycardic, you decide to admit him to the hospital. He is found to be bacteremic and started on iv antibiotics with cefotetan. On the 3rd hospital day , the patient becomes somnolent and later unconscious. A CT scan of his head most likely will showA) a new strokeB) intracranial hemorrhageC) a malignancyD) encephalitis
82 Case 1145-year-old white male embedded as a reporter with the army division that was invading Iraq during 2003, with no previous medical problems, took a break and died. On autopsy, pulmonary embolism was found.Name risk factors for Pulmonary embolism in this case that may have been present.
83 Case 1228 year-old white female who has just given birth 3 weeks previously without complication, develops sudden difficulty breathing while sitting in your treatment chair. Describe your approach to the patient regarding differential diagnosis, acute management and diagnostic strategies.
84 Case 1350-year-old alcoholic man, with known liver cirrhosis and an h/o of esophageal bleeding due to esophageal varies presents for dental work. He has just been diagnosed with head and neck cancer and needs radiation. After evaluation, you determine he needs FME. Complete blood count shows WBC 7500/uL, Hgb 7.5 gm/dL, Hct 22.5%, platelet count 90,000/uL. INR 1.9, aPTT 50 sec.Which parts of the hemostastic system are impaired?Which options do you have to safely perform a FME? Which agents can you use to reverse his “auto-anticoagulation”.
85 Case 14A 52 y/o man is evaluated because of a warm, swollen leg and a history of trauma to the leg 2 weeks ago while on a ski trip in Europe. The leg first became painful on the plane ride home. The patient has mild hypertension that is treated with metoprolol but has no other medical problems. He is not taking any other medications. He is a nonsmoker. There is no family history of thromboembolic disease.What do you think is going on with the patient?What is the next diagnostic step?
86 Case 15Heparin affects which pathway?A) IntrinsicB) Extrinsic
87 Case 16The aPTT is used to monitor anticoagulation with unfractionated heparin. Warfarin is monitored by INR.A) TrueB) False
88 Case 17Explain, how warfarin works, which factors are affected and the reason for individual dosing.
89 Case 18A 38 y/o man is receiving warfarin therapy for DVT of the left leg that he developed 3 weeks ago. He comes in for his scheduled INR check. He denies any gingival bleeding, hematuria, nosebleeds, or gastrointestinal disorder but reports a sore throat and fever that started about 1 week ago. He has not been able to swallow and has consequently been on a mostly liquid diet for the last week.
90 Case 18 cont.On PE: temp 38 C ( 100.4F). His posterior pharynx is erythematous but without exudates. Cardiopulmonary examination is normal. There is 1+ edema of the left leg with tenderness in the popliteal fossa ( improved since 2 weeks ago) and several scattered ecchymoses on the forearms and legs.Labs: Hgb 15, Hct 41% leucocytes 10 K, Platelets 240 INR 6.0 aPTT 37 (normal up to 29)Why is the INR so high?What is the best course of action?
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