To Clot Or not Jason Corbeill PA-C. Thrombus—pathologic blood coagulation –Thrombi “embolize” and travel to new places Clot—the normal coagulation of.

To Clot

Or not

Jason Corbeill PA-C

• Thrombus—pathologic blood coagulation– Thrombi “embolize” and travel to new places

• Clot—the normal coagulation of blood in the healthy body

How to make a clot

• Start the clot– Contact factors

(intrinsic)– Tissue factors

(extrinsic)

• Grow the clot in a specific location

• FAST!!!!!

• Stop the clot– There needs to be a

means for modulating clot production

• Destroy the clot– In an orderly fashion

so as not to cause emboli.

• Normally all of these steps are happening simultaneously throughout the body

• However, there can be a problem with any one of these steps resulting in either excess clot formation (hypercoagulable state) or not enough clot formation (bleeding tendency)

The players

• Starter Growers– Clotting factors– Thrombin– Platelets– VWF– Homocysteine– Lupus anticoagulant

• Anticardiolipin Ab• Antiphospholipid Ab

– Vit K– Factor V Leiden

• Stopper Destroyers– Protein C– Protein S– Antithrombin III– Plasmin– Medications such as

• Heparin• Warfarin• Aspirin/plavix

Sources of Bleeding

• Platelet dysfunction:– Petechiae– bruises

• Clotting factor dysfunction:– Hemorrhage

joints

muscles

Sources of Clot

• Reason for the clot           

• 1. Too many clotting proteins.

• 2. Abnormal clotting proteins.

• 3. Too little thrombolysis.

• 4. Endothelial damage 

• Location of the clot • Arterial = platelet

activation or endothelial damage

• Venous = stasis and factor activation, APS

• Both = abnormal clotting proteins or homocysteine

• Screening tests for hemostasis– CBC/PLT– PT– aPTT– TT

• Tests for prolonged PT or PTT– Mixing studies– Individual factor assays– D-dimer, FDP, fibrinogen-tests for DIC– Lupus anticoagulant– Clot stability assay (F XIII)

• Tests for thrombosis– Protein C&S– Antithrombin III– Factor V Leiden– Homocysteine– Lupus anticoagulant

CASES

Case 1-Mr. D

• 55 y/o male presents with complaint of easy bruising

• Hx?

• PE?

Case 1-Mr. D

• Labs – Cbc normal– PT 20 (12)– PTT 48 (32)– What factor abnormality could cause a

prolonged PT and PTT?

Case 1-Mr D

• Vit K dependent factors:– II, VII, IX, X and protein C and S

Case 1-Mr. D

• Diagnosis: hepatic insufficiency– Lack of production of Vit K– Leads to deficiency of Vit K dependent factors

and protein C and S.

Treat with Vit K (oral, IV, subq)

Case 2-Mr. H

• 35 y/o male presents with chest pain.

• He runs marathons

• Hx?

• PE?

• Cbc normal

• PT normal

• PTT normal

Case 2-Mr. H

Case 2-Mr. H

• What conditions would cause a young, healthy male to be in a hypercoagulable state?– Protein C deficiency– Protein S deficiency– Antithrombin III deficiency– Hyperhomocysteinemia

Case 2-Mr. H

Case 2-Mr. H

• Diagnosis—Hyperhomocysteinemia

• Treatement—vit B6/folate

Case 3-Isabel

• 4 y/o female presenting with rash post URI

• Recent URI lasting 4 days

• Now feels normal

• Little sister is ok

• Hx?

• PE?

Case 3-Isabel

• Labs– WBC 7 (3.5-11.5)– Hgb 13 (12.5-16.5)– PLT 9 (150-300)– PT 11 (12)– PTT 28 (32)

Case 3-Isabel

• ITP-idiopathic thrombocytopenic purpura– Antibodies directed against platelets causing

destruction of platelets in spleenTreatment: platelet transfusion if bleeding or

less than 10k. Steroids/IVIG, splenectomy

? What would you have to include in your differential diagnosis if she was older, had confusion or AMS and creatinine (CR) was 2.5 (elevated)?

Case 4-Mrs. D

• 30 y/o female with metastatic breast cancer

• Admitted for left leg pain, found acetabular bony mets and fractures.

• This am on rounds, noticed left lower extremity edema 2-3+, dusky.

• Labs: CBC, PT, PTT normal

Case 4-Mrs. D

• DVT– Virchow’s triad-hypercoagulable state, venous

stasis, intimal trauma– More Labs: D dimer positive but not very

specific.– Treatment: anticoagulation (put the brakes on

the cascade), elevate, compression stockings, hydration, IVC filter

Case 4-Mrs. D

• Try to avoid this…

Case 5-Howie

• 5 y/o with scalp wound that isn’t healing well-just keeps oozing.

• Has had delayed wound healing all of his life, bled more than expected with circumcision.

• Little brother seems to have similar problem

Case 5-Howie

• Family History: mother’s father died of bleeding ulcer age 49

• PE:

• Labs: – PT 11 (12)– PTT 54 (32)– Cbc normal– More labs?

Case 5-Howie

• Tests for prolonged PT or PTT– Mixing studies– Individual factor assays– D-dimer, FDP, fibrinogen-tests for DIC– Lupus anticoagulant– Clot stability assay (F XIII)

Case 5-Howie• Mixing studies:• Barium sulfate absorbed plasma: • lacks II, VII, IX and X, but • contains I, V, VIII and XIII. • Serum: • lacks I, V, VIII, and XIII, but • contains II, VII, IX and X.

• Modification  PTT   Ref   • Pt + barium sulfate abs plasma  53  (22-34) • Pt + serum 24   (22-34)

Case 5-Howie

• Factor IX deficiency (Hemophilia B)– Factors II and X are in common pathway and

their deficiency would cause both PT and PTT elevation.

– Factor VII is in the extrinsic pathway and it’s deficiency would cause elevated PT as well.

– So it must be factor IX deficiency

Case 5-Howie

• Hemophilia A (factor VIII) deficiency

• Hemophilia B (factor IX) deficiency– X linked recessive– Severity depends on how much factor

Treatment: Factor IX concentrates after wounds and prior to surgery

Case 5-Howie

Case 6-Mrs. R

• 35 y/o female presenting with joint stiffness, right leg pain and edema

• Hx fetal loss x 2

• Maternal grandmother died of “blood clot in the lung” at age 40

Case 6-Mrs. R

– PT 11 (12)– PTT 48 (32)– WBC  12.4 (3.5-11.5)     – Hgb 13.3 (12.5-16.5)– PLT  118 (130-440)– RF 126 (0-40)– ANA 1:80 (neg)

Case 6-Mrs. R

• Antiphospholipid Antibody Syndrome?– PTT prolonged in vitro only, patient is actually

hypercoagulable– PTT will not correct with mixing study– Lupus anticoagulant– Check Anticardiolipin Ab– Anti beta 2 glycoprotein-I– ANA positive– Anti ss DNA– Antiphospholipid antibodies

Case 6-Mrs. R

• Treatment: – Heparin to coumadin. – Goal INR over 3.– What about the thrombocytopenia?

• Due to APL Ab binding to phospholipid on platelet cell surfaces.

Case 7-Mrs. KL

• 28 y/o female presents with easy bruising

• Bleeds excessively with dental procedures

• History of menorrhagia

• Pregnant with her first child

• FH significant for bleeding problems– Male and female – Scared because her aunt supposedly died in

childbirth due to hemorrhage

Case 7-Mrs. KL

• Labs:– PT 11.2 (12)– PTT 42 (32)– WBC 11.2 (3.5-11.5)– Hgb 11.2 (12.5-16.5)– PLT 160(130-440)

Case 7-Mrs. KL

• ? Von Willebrands Disease?• Autosomal dominant

– VWF is produced in the endothelial cells and platelets– Promotes platelet adhesion to endothelial cells and

each other– Labs include

• VWF antigen (decreased) – Level of VWF

• Ristocetin cofactor activity (down) – Measurement of the activity of VWF

Case 7-Mrs. KL

• Why is PTT prolonged?– VWF also binds to FVIII to create a complex

which ultimately promotes the conversion of X to Xa.

– Decreased function of F VIII (as in hemophilia A)

Case 7-Mrs. KL

• Treatment:– Factor VIII concentrates– DDAVP (desamino-D-arginine vasopressin)

• Promotes the production of VWF

Case 8-Mr. P

• 22 y/o male hotel clerk presents with chest pain, sob, hemoptysis.

• VS: BP 138/88 R 36 P 96

• Exam: CTA

• ABG– PO2 83 (80-100)– PCO2 26 (35-45)– pH 7.28 (7.36-7.44)

Case 8-Mr. P

• So, Mr. P has a pulmonary embolism.

• CT shows it but you susupected it sooner and have already given him heparin/LMWH.

• Why does he have a PE?

Case 8-Mr. P

• Reason for the clot           

• 1. Too many clotting proteins.

• 2. Abnormal clotting proteins.

• 3. Too little thrombolysis.

• 4. Endothelial damage 

• Location of the clot • Arterial = platelet

activation or endothelial damage

• Venous = stasis and factor activation, APS

• Both = abnormal clotting proteins or homocysteine

Case 8-Mr. P

• PT 11 (12)

• PTT 29 (24-34)

• CBC normal

Tests for thrombosis– Protein C&S– Antithrombin III– Factor V Leiden– Homocysteine– Lupus anticoagulant

Case 8-Mr. P

• Factor V Leiden– Leiden is an abnormal Factor V protein

• It is unable to be inhibited.• 5% of the caucasian population has Factor V

Leiden (1:20)• Heterozygotes 7x increased risk clot• Homozygotes 80x increased risk of clot

statistic

• 60% of inherited hypercoagulable states are due to:

• Factor V Leiden

• Prothrombin polymorphism

• Mutations of Protein C, S and antithrombin III

Case 8-Mr. P

• Lifelong coumadin