Hemodynamics / hemostasis disorders

Question 1

post partum mother presents with SOB, neurologic symptoms, and increased bleeding time.
what can be found in the emboli?

poma 38, FA 609

Answer 1

amniotic fluid emboli, can find squamous cells, keratin debris, and thromboplastin (tissue factor, factor VII)
Can cause DIC

Question 2

pt with increased bleeding time has lab findings of schistocytes, elevated D dimer, and decreased fibrinogen.
give a few examples that could cause this widespread disease?

FA 398, poma 35

Answer 2

this is disseminated intravascular coagulation
causes include 
GRAM NEGATIVE Sepsis especially E coli or N meningitidis, 
Trauma, 
Obstetric complications, 
acute Pacreatitis
Malignancy
Nephrotic syndrome
Transfusion
STOP Making New Thrombi

Question 3

How does aspirin decrease platelet aggregation?
What is the main mechanism of platelet aggregation?

FA 387, poma 31

Answer 3

Inhibits COX inside platelets so that platelets cannot make TXA2 / thromboxane, which promotes platelet aggregation.
GPIIb/IIIa binds platelet-to-platelet via fibrinogen.

Question 4

what are the three treatments for immune thrombocytopenic purpura and their mechanism?

FA 397, poma 32

Answer 4

Steroids to decrease immune response.
IVIG to make splenic MQ’s eat that Ig instead of the platelet-bound-Ig antibodies.
Splenectomy to get rid of the source of IgG AND the destruction of platelets.

Question 5

Female pt with autoimmune disorders presents with petechiae. findings are schistocytes on blood smear and low platelet count.
what is the most common mechanism of thrombic thrombocytopenic purpura?

FA 397

Answer 5

autoantibody against ADAMTS13, which normally cleaves vWF multimers into smaller monomers for degradation.
if not cleaved, they result in abnormal platelet aggregation and micoangiopathic hemolytic anemia.

Question 6

child eats undercooked beef. develops mucousy bowel.
he develops thrombocytopenia with increased bleeding time, and schistocytes are seen on histo. NL PT/PTT.
what is the mechanism of this bacterial infection?
what other organ system will it damage?
FA 172, poma 33

Answer 6

pt is infected with E coli O157:H7; its verotoxin damages endothelial cells resulting in platelet microthrombi -> hemolytic uremic syndrome (HUS) which will cause renal damage (more commonly) and CNS damage.

Question 7

pt presents with easy bruising. findings are large platelets, mild thrombocytopenia, and no agglutination is seen on ristocetin cofactor assay.
what mechanism of hemostasis is defective?
FA 397, poma 33

Answer 7

Defective GPIb deficiency genetically, which results in decreased platelet ADHESION to endothelium.
GPIb binds to vWF expressed on damaged endothelium.
Bernard-Soulier syndrome

Question 8

platelet to platelet aggregation is defective.
what is mechanism?
what symptoms can be seen?
FA 397, poma 33

Answer 8

GpIIb/IIIa is defective, resulting in inability for platelets to aggregate together using fibrinogen.
Will see petechiae, purpura, epistaxis.
Glanzmann thrombasthenia

Question 9

what does PT measure?
what does PTT measure?
what antithrombotic drug would we test for each
FA 397, poma 34

Answer 9

PT: extrinsic pathway, factor VII. coumadin / warfarin
PTT: intrinsic pathway, factor XII, XI, IX, VIII. HEParin

Question 10

PTT is elevated, PT is NL
what factor could be affected by an X-linked recessive mutation?
what are the classical symptoms?
FA 397, poma 34

Answer 10

FVIII
hemophilia A
Symptoms include deep tissue bleeding, hemoarthrosis, and post surgical bleeding.
bleeding time is NL.

Question 11

difference between hemophilia B and A?

FA 397, poma 34

Answer 11

Same except hemophilia B is decrease in F IX (christmas), and hemophilia A is F XIII.
same symptoms, both X linked recessive.

Question 12

patient with elevated PTT is given a mixed study; their plasma is mixed with NL plasma for suspected hemophilia A however PTT does not improve.
what could be the cause?
poma 34

Answer 12

coagulation factor inhibitor; antibody against FVIIII
if hemophilia A, mixing NL plasma with pt’s plasma would improve PTT because you’re giving VIII

however in anti-FVIII, antibodies override and the mix study does not help.

Question 13

Patient presents with petechiae, musosal bleeding and frequent epitaxic episodes.
Bleeding time is elevated, and a platelet adhesion or platelet aggregation issue is suspected.
Ristocetin test however shows platelet agglutination.
What is the diagnosis?

FA 397-398, poma 34

Answer 13

Glanzmann thrombasthenia.
Why?
Petechiae, epistaxis -> primary hemostasis disorder (so platelet quantity or quality, plugging)
Ristocetin test is for intact vWF and GP1b. If these two are intact, the next platelet aggregation problem is GpIIb/IIIa!
so it is NOT von willebrand disease OR Bernard-Soulier.

Question 14

Ristocetin test shows no agglutination.
Is this nL or abnl?
What are your differentials?

FA 397, 398. poma 34

Answer 14

Bernard-Soulier (defective GP1b) vs von Willebrand disease (defective vWF)

Ristocetin tests the platelet agglutination by causing vWF to bind to platelet GP1b

Question 15

How does desmopressin treat von Willebrand disease?

FA 398, poma 34

Answer 15

(ADH analog) increases vWF release from Weibel-Palade bodies of endothelial cells

Question 16

Mechanism of Warfarin in decreasing clot formation?
Why does it increase PT time?

FA 386, 406

Answer 16

Warfarin inhibits enzyme vitamin K epoxide reductase in the liver.

Vitamin K is required for the gamma carboxylation of factors II, VII, XI, and X, and proteins C and S.
PT is dependent on Factor VII therefore increased PT time (extrinsic) is seen.

Question 17

How could an elevated PTT be seen in a patient with von Willebrand disease?

FA 398, poma 34

Answer 17

vWF stabilizes F VIII, which is part of the intrinsic / PTT pathway.
this means that in some patients, elevated PTT can be seen.

Question 18

A patient who was on prolonged antibiotic use presents with hemoarthrosis. Elevated PT is found.
What mechanism could explain findings?

FA 386, poma 35

Answer 18

Patient has vitamin K deficiency due to destruction of NL gut microflora, which synthesis vitamin K.

Vitamin K - via epixide reductase - is activated in liver and is crucial for gamma carboxylation of factors II, VII, IX, and X.
Therefore, patient will present with symptoms of coagulation deficiency and have elevated PT due to factor VII not being synthesized.

Question 19

A patient on heparin therapy develops decreased platelet count.
What autoimmune process could develop?
Should we replace them on warfarin?
FA 405, poma 35

Answer 19

Pt has developed IgG antibodies against Heparin-FIV complexes, and MQ’s now phagocytose platelets.
Complication is thrombosis via platelet fragments.

These patients have increased risk of warfarin skin necrosis, so use another anticoagulant.

Question 20

A patient post infection presents with increased bleeding time, elevated PTT/PT are found which means clotting factors are destroyed.
D-Dimer however is found to be nL, and there is a nL platelet count.
What is the diagnosis and what are two etiologies?

FA 398, 386, poma 36

Answer 20

The patient is presenting with symptoms similar to DIC however no fibrin or clots were ever made, because D-dimer and platelet counts are NL.

therefore, it is a fibrinolysis disorder, and fibrinogen split products are found instead due to pathologic plasmin activation.

Due to 1) urokinase release post-prostatectomy
2) liver cirrhosis leading to decreased alpha2-antiplasmin

Question 21

Patient presents with frequent vessel thrombosis, intellectual disability, long slender fingers, and lens subluxation.
What will likely be elevated in the urine?
Why the increase in thrombosis?

FA 108, poma 37

Answer 21

Pt has cystathionine beta synthase deficiency -> increased homocysteine

Homocystinuria.

Homocysteine damages endothelium, which is 1 of Virchow’s Triad.

Question 22

High homocysteine levels are found in a pt who developed atherosclerosis.

What vitamin could they be deficient in?

FA 108, poma 37

Answer 22

Either Folate or B12 deficiency

both are required for the conversion of homocysteine to methionine

Question 23

A pt in hypercoagulable state is quickly started in Warfarin.
Pt shortly develops a patch of skin necrosis.
What pre-existing genetic condition could this pt have that increased the risk of this toxicity?
What drug treatment should have been given with Warfarin?

FA 398, 405, poma 37

Answer 23

Increased risk of skin necrosis with hemorrhage folowwing administration of warfarin.
Skin necrosis after warfarin administration ->think protein C deficiency. (FA 398)

Protein C and protein S have shorter half-lives than 2, 7, 9, and 10, resulting in early transient hypercoagulability with warfarin use (which blocks epoxide reductase which activates vit K) (FA 405)

Heparin “bridging” to activate antithrombin.

Question 24

Pt presents with h/o frequent DVT’s.
What is the most common cause of inherited hypercoagulability in whites?
What is the mechansim?

FA 398

Answer 24

Factor V Leiden deficiency.

Mutant FV is resistant to degradation by activated Protein C.

Question 25

Pt presents with frequent clots. Blood work findings show extremely elevated levels of prothrombin.
What is the gene mutation? What is the mechanism?

FA 398, poma 37

Answer 25

Prothombin gene mutation 20210A

Thrombin cleaves fibrinogen into fibrin, increasing thrombosis.

Question 26

Pt is started on Heparin. PTT is used to monitor however it does not increase.
What is the diagnosis if it is i) genetic or ii) acquired, and mechanism?

FA 386

Answer 26

Inherited deficiency of antithrombin: has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following Heparin administration (FA 398, poma 37)

Can also be acquired: nephrotic syndrome -> antithrombin lost in urine.

Heparin enhances the activity of antithrombin (FA 386)

Question 27

How does Heparin raise PTT?

Answer 27

Heparin enhances effects of antithrombin.

Antithrombin inhibits activated forms of factors 2, 7, 9, 10, 11, 12, all part of PTT. (FA 386)

Question 28

Pt presents with petechial rash to chest and hypoxia.
Denies recent bone fracture but did have liposuction surgery last week.
Diagnosis?

Answer 28

Fat emboli. FA 609

Question 29

Pt presents with pleuritic chest pain, tachycardia, slight fever. Is hypoxic and is in respiratory alkalosis.

What are common lab findings?

Answer 29

V/Q mismatch on V/Q scan
Spiral CT showing vascular filling defect
Lower extremity doppler showing DVT (MCC of embolism)
Elevated D-Dimer due to fibrinolysis of clots -> fibrin split products
FA 609, poma 39

Question 30

Caisson Disease
Describe symptoms
Cause
what is decreased in the blood stream?

Answer 30

Diver comes up to quickly
Pressure N2 decreases in the blood because it becomes nitrogen bubbles.
Causes the “bends” and can cause osteonecrosis
FA 426, FA 609

Question 31

NL platelet count

what is thrombocytopenia

Answer 31

150-400 K/uL

Question 32

megakaryocytes seen on BM biospy

Answer 32

platelets are being destroyed, so they are trying to make more
immune thrombocytopenic purpura