Transcript Background - Lock Haven University of Pennsylvania

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
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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
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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 spleen
Treatment: 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
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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
• Pt + barium sulfate abs plasma
• Pt + serum
PTT Ref
53 (22-34)
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
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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