Introduction to thrombosis [email protected] Assistant Professor of Medicine...

Introduction to thrombosis

[email protected]

Assistant Professor of Medicine

Hematology/Oncology2014

Objectives

1. Arterial Thrombosis: -Pathophysiology, Risk factors,

Symptoms and Signs, treatment 2. Venous Thrombosis:-Pathophysiology, Risk Factors,

Symptoms and Signs 3. Common anticoagulants 4. Hereditary and acquired

Hypercoagulable Disorders

Summary of Hemostasis

Platelet plug forms

Stabilization byfibrin formation(clotting cascade)

Extension of clotlimited by:

Natural anticoagulants

Fibrinolysis

Arteries versus Veins

Thick,muscular

Thin, pliable

High pressure

High oxygen

Low pressure

Low oxygen

Exception: pulmonary artery –O2 low

Blood ClottingArterial Venous

Plateletsmore important

Blood clotting factorsmore important

Pathogenesis

Atherosclerosis is a slow process that starts in childhood and results in occlusion of arterial blood vessels

Interruption 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)

Risk factors for arterial thrombosis

Smoking HTN cholesterol diabetes Homocysteine ? obesity sedentary life style Advanced age Family History Inflammation

Endothelial dysfunction

Fatty streak

Soft plaque

Hard plaque

Plaque rupture

Thrombosis/Occlusion

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 weakness 3. Peripheral Vascular Disease (PVD),

chronic versus acute-sudden onset of severe pain, palor, cold skin ( No pulse palpable)

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 ASA

No role for warfarin Risk factor modification important

Objectives





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 ED

CT Chest with PE protocol shows:

Case #2

A 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 Chemotherapy

He undergoes placement of a PICC line R arm

3 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

Case #3

A 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 ago

US Doppler shows acute DVT extending from her popliteal vein into her femoral vein covering the entire thigh

CT Chest by PE protocol shows PE in the RLL with signs of early infarction.

Venous Thromboembolism (VTE) Incidence and Impact in the United States

Approximately 2 million VTEs occur every year1

Each year 1 person in 1,000 will experience his/her first VTE in the US2

One 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 cases

Recurrent DVT: ~17% of DVT patients 2 years after initial

treatment*3

~30% of DVT patients 8 to 10 years after initial treatment*†3,4

1. Hirsh J, Hoak J. Circulation. 1996;93:2212-2245. 2. American Heart Association. Heart Disease and Stroke Statistics – 2004 Update. 3. Prandoni P et al. Haematologica. 1997;82:423-428. 4. Pengo V et al. N Engl J Med. 2004;350:2257-2264.

*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.

NBC News Correspondent David Bloom. While covering thewar 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”

Venous thrombosis-Clinical Manifestations

1. Extremities, Deep venous thrombosis (DVT)

Swelling, Redness/dusky color, warmth

sudden onset vs. gradual

2. Pulmonary embolism (PE)

SOB, acute versus gradual

Diminished exercise capacity

chest pain syncope cardiac

arrest/deathLess common sites: Portal vein, renal vein,cerebral sinus vein

PE: Clinical Presentation

Symptom or Sign Percent

Dyspnea 82

Respiratory Rate >20/min 60

Heart Rate >100 beats/min 40

Chest pain 49

Cough 20

Syncope 14

Hemoptysis 7Goldhaber SZ, et al. Lancet 1999.

Most Common Sx/Si Among 2454 Pts in International Cooperative Pulmonary Embolism Registry

Goldhaber SZ, et al. Lancet 1999.

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

Venous thrombosis-Pulmonary embolism

Part of the thrombus can break off and travel through major veins, right heart into pulmonary artery until it becomes lodged

Blood 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 dysfunction

Increased airway resistance d/t bronchoconstriction

Decreased pulmonary compliance If clot burden is high ( saddle embolus-both PA

affected): cardiovascular arrest and death

ALTERED VESSELS ~inflammatory damage ~mechanical injury ~hypoxia

VENOUS STASIS ~immobility ~paralysis ~reduced flow states

ALTERED COAGULABILITY ~inflammatory stimuli ~consumption of endogenous anticoagulants

Virchow’s Triad

Risk Factors for Venous Thrombosis

Common: Trauma Post-surgery Immobility/Inactivity Obesity Pregnancy Estrogens/Birth control Malignancy Age Previous history of DVT/PE

Age and VENOUS THROMBOSIS

AGE

RIS

K O

F T

HR

OM

BO

SIS

1:100,000

1:1000

1:100

40 y.o. 75 y.o.

1:10,000

Risk Factors for Venous Thrombosis

Inherited procoagulant disorders

-Factor V Leiden-Prothrombin gene

mutation-Protein C deficiency-Protein S deficiency-Antithrombin deficiency

Acquired 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

Diagnosis of venous thrombosis

Symptoms

Blood work -elevated D-Dimer-Negative D-Dimer rules out thrombosis

Imaging for Limb: -Compression ultrasonography +/-US-Doppler,

Imaging for Lungs:-CT scan-VQ scan

Hypercoagulable States

Defect Incidence in Population

Percent of Patients with Procoagulant

States

Factor V Leiden 5-10% 20-60%

Prothrombin Gene Mutation 2-4% 6-8%

Homocysteinemia -- 10%

Protein C Deficiency 1:200 <5%

Protein S Deficiency -- <5%

Antithrombin Deficiency 1:2-5,000 <1%

Dysfibrinogenemia Not known ~1-2%

Known Malignancy 16-18%

Treatment of acute DVT/PE

Treatment for acute clot is heparin Heparin inactivates activated clotting

factors (clotting cascade initiated) Minimum time: 5 days and until warfarin

is fully therapeutic -overlap heparin with therapeutic INR x 2 days Warfarin used to prevent additional clots Warfarin 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

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

Bates, S. M. et al. N Engl J Med 2004;351:268-277

Objectives





Anticoagulants

Unfractionated Heparin

LMWH-enoxaparin ( Lovenox)-Dalteparin (Fragmin) Direct Xa inhibitor-Fonaparinux ( Arixtra) Vitamin K

antagonist-Warfarin (Coumadin)

New oral anticoagulants

Direct thrombin inhibitor

Dabigatran ( Pradaxa) Anti-Xa inhibitors-Rivaroxaban ( Xarelto)-Apixaban (Eliquis)

The Heparin Family

N-acetylglucosamine 6-O-sulfate

Glucuronic acid

N-sulfated glucosamine3,6-O-disulfate

Iduronic acid2-O-sulfate

N-sulfatedglucosamine6-O-sulfate

UFH LMWH PENTASACCHARIDE (Fondaparinux)

Mechanism of Action - UFH

UFH

5-sugarsequence

Factor Xa

Factor IIa

Factor Xai

Factor IIai

Antithrombin

Mechanism of Action - LMWH

LMWH

5-sugarsequence Factor Xa

Antithrombin Factor Xai

Warfarin

Interferes with carboxylation of vitamin K dependent factors

Factor II (thrombin), VII, IX, X,

protein C, protein S Prothrombin Time (PT)/INR is used

to monitor warfarin because half life of Factor VII is the shortest (5-7 hours)

Warfarin

Synthesis of Non

Functional Coagulation

Factors

Also affects Protein C

and protein S

Antagonismof

Vitamin K

Warfarin Mechanism of Action

Vitamin K

VII

IX

X

II

0

20

40

60

80

100

0 1 2 3 4 5 6

Days

Fac

tor

acti

vity

(%

)Factor VII Factor IX Factor X Factor II

Effect of Warfarin on Factor Activity

Therapeutic INR once ALL factors suppressed

Mechanisms of Anticoagulation1

1. Adapted with permission from Petitou M et al. Nature. 1991;350(suppl):30-33; http://www.nature.com/2. Hirsh J, Fuster V. Circulation. 1994;89:1449-1468.3. 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.

XIIa

IIa

Xa

Intrinsic system(surface contact)

XII

XI XIa

Tissue factor

IX IXa VIIa VII

VIII VIIIa

Extrinsic system(tissue damage)

X Xa

V Va

II

Fibrinogen Fibrin

(Thrombin)IIaFactor Xa inhibitors4,5

Direct thrombin inhibitors4,5

Vitamin K antagonists4

Heparins2,3

INR – Oral (warfarin) anticoagulation

Therapeutic Range INR 2.0-3.0

(Most situations) Mechanical Heart Valve INR

2.5-3.5

Dose:Diet (Vitamin K)MetabolismConcurrent medications

**The higher the INR the higher the bleeding risk

Drug Interactions

Management of excessive anticoagulation

Depends on INR level and presence of bleeding symptoms

Options: Hold warfarin dose until INR is in therapeutic

range Give Vitamin K (po, im, iv), if patient not

bleeding-takes 24-48 hours Give 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 immediately Recombinant Factor VII if all else fails ( caution:

thrombogenic!)

Antithrombotic Characteristics

Drug Half-LifeDuration of

effectRenal

clearance?Reversal

UFH(sq BID-TID) 1-2 hrs 8-12 hrs No Protamine

LMWH(sq q day-BID) 4-7 hrs 12-24 hrs

Yes(>30 ml/min)

±Protamine (40-70%)

Warfarin(po daily) 20-60 hrs 48-72 hrs No

FFPVitamin K

Fondaparinux(sq daily) 17-21 hrs 24 hrs

Yes(>30 ml/min)

None(VIIa conc?)

Dabigatran12-17 hrs 24-36 hrs

Yes(>30 ml/min)

None(Dialysis)

Rivaroxaban

5-9 hrs 24 hrs yes None

New anticoagulants-No monitoring

Dabigatran (Pradaxa): oral direct thrombin inhibitor

FDA approved in US for Atrial fibrillation, 150 mg po bid

slightly less bleeding risk than warfarin

Rivaroxaban (Xarelto): oral Factor Xa inhibitor

FDA approved for A fib ( 20 mg qd) and DVT/PE treatment, 15 mg bid x 3 weeks, then 20 mg qd

Apixaban (Eliquis): oral Factor Xa inhibitor 5 mg po bid for non-valcular A fib Increased risk of stroke after stopping drug

(Rebound)

Bridging case

45 y/o female PMH:

HTN ‘idiopathic’ DVT in 2005, PE in 2/2008-

20 days after leg injury. Antiphospholipid-Antibody syndrome

(APLS)=severe hypercoagulable disorder

Chronic warfarin therapy (since 2/08) without complications

Oh by the way…

Scheduled for FME in 7 days and was instructed to stop warfarin tomorrow.

Bridging

Use of parenteral anticoagulants during period of withholding warfarin therapy e.g. colonoscopy, surgery, multiple

dental extraction Parenteral anticoagulants: heparin, low

molecular weight heparin (LMWH), Minimize period of time without

anticoagulation

Typical bridging protocol

5 days before procedure-stop warfarin (pm dose)

3 days before procedure start LMWH ( am injection)

No LMWH on morning of procedure Restart LMWH within 24-48 hrs after

procedure Start warfarin on the evening of

procedure: remember that is takes several days before warfarin is at therapeutic levels

Follow INR and stop LWMH once INR is at target

Anticoagulation clinics/PCP

What’s this patient’s risk of having thrombotic event off

anticoagulation?a. Low

b. Moderate

c. High

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 position

PLAN: - stop warfarin 4-5 days before surgery, allow

INR to return to normal. Use postoperative prophylaxis and simultaneously begin warfarin

Intermediate risk of thromboembolism

Mechanical Heart Valve Bileaflet (St. Jude) aortic valve and one:

A.fib, prior CVA/TIA, DM, HTN, HF, age >75 Atrial Fibrillation

CHADS-2 score of 3 or 4 VTE within past 3 to 12 mo

Non-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 LMWH

CHADS-2: CHF, HTN, age >75, DM, prior TIA/CVA

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 disease

PLAN: -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 12-24 hrs before surgery

Managing patients on anticoagulation requiring invasive

procedures-alternative option Low risk of bleeding Continue warfarin at lower dose and operate at an INR of

1.3-1.5 Intensity has been shown in RCT to be safe in gynecologic

and orthopedic surgery patients Dose of warfarin can be lowered 4-5 days preop Warfarin therapy can be restarted at regular doses

postoperatively, supplemented with low dose UFH or prophylactic LMWWH

Anticoagulants for Bridging

Therapeutic dose (DVT/PE treatment dose) enoxaparin (Lovenox)1 mg/kg SQ bid or

1.5 mg/kg/day dalteparin (Fragmin)200 IU/kg/day or 100

IU/kg/bid Unfractionated heparin with therapeutic

APTT (61-84 sec) Low dose

enoxaparin 30 mg SQ twice daily or 40 mg SQ once daily

dalteparin 2500 or 5000 units SQ once daily

Bridging Plan - LMWH Stop warfarin approximately 5 days prior to

procedure (Grade 1B) Initiate LMWH once INR below therapeutic level

Usually day 4 or 3 prior Last 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)

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.”1

Grade 1B recommendation: continue warfarin around time of minor dental procedure (single or multiple tooth extraction and root canal procedure)2

1. Arch Intern Med 1998;158:1610-6 2. Chest 2008;133:299S

Objectives




hypercoagulable Disorders

Indications of a congenital Defect in a patient with

thrombosis First thrombosis age <50 Family history of thrombosis Recurrent episodes of thrombosis Thrombosis at unusual sites Neonatal thrombosis Thrombosis without apparent

antecedent thrombogenic event

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 II

3. Deficiencies of Antithrombin III (AT III), Protein S and Protein C

-Reduced amounts of natural anticoagulants leads to imbalance in the clotting cascade

How common are these disorders?

Case #2 19 y/o healthy and

active woman is evaluated for swollen RLE x 5 days in local ER

Started on birth control 5 mo prior

US shows Right popliteal DVT

“Hypercoag panel” drawn at time of presentation:

Heterozygous for Factor V Leiden

Issues: Long-term

management Pregnancy Surgeries Genetic counseling

(siblings, children)

Factor V Leiden

Autosomal dominant genetic mutation (1994 in the Dutch city of Leiden)

This is not a deficiency! but a structural change in the Factor V

Diagnosis by DNA analysis ( heterozygotes vs homozygotes)

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 generation

2. 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)

Factor V Leiden Mechanism

TF+ VIIa

IX+VIII

X+V (=abnormal)

II

Fibrinolysis CLOT

Antithrombin

Protein C and

Protein S

Degradation of Factors V, VIII

Prothrombin gene mutation

PG20120A (Factor II mutation) genetic polymorphism that causes

increased amount of prothrombin (factor II) in the circulation

occurs in ~2-3% of Caucasian population in the U.S.

associated with VENOUS thrombosis at least half of clotting events

precipitated by some stimulus most people with the mutation DON’T

clot

Testing for prothrombin gene mutation

DNA analysis for prothrombin G20210A mutation Distinguishes heterozygotes and

homozygotes

What is the risk of thrombosis?

Deficiencies of natural anticoagulants

Leads to imbalance between coagulation and anticoagulation

Natural anticoagulants: Protein C,S and Antithrombin deficiency

Patients present early in life, usually with venous thrombosis

Often additional risk factors are present

Natural Anticoagulants: AT III, protein C, S

TFPI TF+ VIIa

IX+VIII

X+V

II

Fibrinolysis CLOT

Antithrombin

Protein C and

Protein S

Heparin

Degradation of Factors V, VIII

Protein C/S deficiency

Asymptomatic carriers Thrombosis is a multi-risk disorder Additional risk factors are often required

to cross the thrombosis threshold Some carriers will never have a

thrombotic event Asymptomatic family members rarely

need anticoagulation Prophylaxis during high risk events:

pregnancy, surgery or immobilization Estrogen therapy ( OCP, perimenopausal)

is contraindicated-use anticoagulation

Acquired hypercoagulable States

Malignancy Presence of a central venous catheter Surgery, especially orthopedic Trauma Pregnancy Oral contraceptives Hormone replacement therapy or Tamoxifen, Anti-angiogenesis (Bevacizumab,

Thalidomide,Lenalidomide) Congestive heart failure

Antiphospholipid antibody syndrome Myeloproliferative disorders (Polycythemia vera, Essential

thrombocythemia) Paroxysmal nocturnal hemoglobinuria (PNH) Inflammatory bowel disease Nephrotic syndrome Hyperviscosity (Waldenstrom's macroglobulinemia,

Multiple myeloma) Marked leukocytosis in acute leukemia Sickle cell anemia HIV/AIDS

Antiphospholipid Antibody Syndrome

Acquired hypercoagulable state Presence 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 recommended

Need to “bridge” before procedures

Case #3 40 y/o female presents with idiopathic DVT

LLE/PE at the age of 35 Treatment with heparin/ warfarin x 6 months Does well until 2 years later when she presents

with recurrent PE, anticoagulation restarted 7 months later she has a 3rd PE while therapeutic

on warfarin (INR at 2.5), Filter placed, O2 dependent

Hypercoagulable panel shows very high titers for Antiphospholipid antibodies

Goal INR is raised to 3-4 6 months later, she develops DVT in RLE while

on warfarin, gets transitioned to twice daily LMWH injections

Cancer is a hypercoagulable state

5-10% of patients presenting with idiopathic VTE will be diagnosed with cancer in the next 12-24 months 1

VTE has been found in 20-50% of cancer patients at autopsy 2

Cancer patients have higher rates of recurrent VTE and bleeding than patients without cancer3,4,5

Cancer patients with VTE have higher mortality than those without VTE 6

1 J Thromb and Haemost 2004;2: 885 2 Am J Med Sciences 1938; 34: 566 3 JCO 2000;18: 3078 4 Medicine 1999;78: 285 5 Blood 2002; 100: 3484 6 NEJM 2000; 343: 1846

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 recurrence

Alternative: warfarin

Need bridging if on warfarin.

Questions??

Dental case studies

[email protected]

Assistant Professor of MedicineHematology/Oncology

mailto:[email protected]

mailto:[email protected]

Case 8

A 66 y/o male with atrial fibrillation and no prior stroke, otherwise healthy, comes in for dental extraction. You should

A) stop coumadin 4-5 days beforeB) lower his dose for 4-5 days to achieve an

INR of 1.3-1.5 and proceed with extraction

C) Bridge the patient with LMWH after he stops coumadin 4-5 days before

D) Bridge the patient with UFH after he stops coumadin 4-5 days before

Case 9

A 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 week

C) Postpone implantsD) Stop Coumadin, place temporary filter

and proceed with implants. Have his PCP restart anticoagulation.

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 show

A) a new stroke B) intracranial hemorrhageC) a malignancyD) encephalitis

Case 11

45-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.

Case 12

28 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.

Case 13 50-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”.

Case 14 A 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?

Case 15

Heparin affects which pathway?A) IntrinsicB) Extrinsic

Case 16

The aPTT is used to monitor anticoagulation with unfractionated heparin. Warfarin is monitored by INR.

A) TrueB) False

Case 17

Explain, how warfarin works, which factors are affected and the reason for individual dosing.

Case 18

A 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.

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?

Introduction to thrombosis [email protected] Assistant Professor of Medicine...

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