Hemodynamics / hemostasis disorders Flashcards
post partum mother presents with SOB, neurologic symptoms, and increased bleeding time.
what can be found in the emboli?
poma 38, FA 609
amniotic fluid emboli, can find squamous cells, keratin debris, and thromboplastin (tissue factor, factor VII)
Can cause DIC
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
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
How does aspirin decrease platelet aggregation?
What is the main mechanism of platelet aggregation?
FA 387, poma 31
Inhibits COX inside platelets so that platelets cannot make TXA2 / thromboxane, which promotes platelet aggregation.
GPIIb/IIIa binds platelet-to-platelet via fibrinogen.
what are the three treatments for immune thrombocytopenic purpura and their mechanism?
FA 397, poma 32
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.
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
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.
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
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.
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
Defective GPIb deficiency genetically, which results in decreased platelet ADHESION to endothelium.
GPIb binds to vWF expressed on damaged endothelium.
Bernard-Soulier syndrome
platelet to platelet aggregation is defective.
what is mechanism?
what symptoms can be seen?
FA 397, poma 33
GpIIb/IIIa is defective, resulting in inability for platelets to aggregate together using fibrinogen.
Will see petechiae, purpura, epistaxis.
Glanzmann thrombasthenia
what does PT measure?
what does PTT measure?
what antithrombotic drug would we test for each
FA 397, poma 34
PT: extrinsic pathway, factor VII. coumadin / warfarin
PTT: intrinsic pathway, factor XII, XI, IX, VIII. HEParin
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
FVIII
hemophilia A
Symptoms include deep tissue bleeding, hemoarthrosis, and post surgical bleeding.
bleeding time is NL.
difference between hemophilia B and A?
FA 397, poma 34
Same except hemophilia B is decrease in F IX (christmas), and hemophilia A is F XIII.
same symptoms, both X linked recessive.
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
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.
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
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.
Ristocetin test shows no agglutination.
Is this nL or abnl?
What are your differentials?
FA 397, 398. poma 34
Bernard-Soulier (defective GP1b) vs von Willebrand disease (defective vWF)
Ristocetin tests the platelet agglutination by causing vWF to bind to platelet GP1b
How does desmopressin treat von Willebrand disease?
FA 398, poma 34
(ADH analog) increases vWF release from Weibel-Palade bodies of endothelial cells
Mechanism of Warfarin in decreasing clot formation?
Why does it increase PT time?
FA 386, 406
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.
How could an elevated PTT be seen in a patient with von Willebrand disease?
FA 398, poma 34
vWF stabilizes F VIII, which is part of the intrinsic / PTT pathway.
this means that in some patients, elevated PTT can be seen.
A patient who was on prolonged antibiotic use presents with hemoarthrosis. Elevated PT is found.
What mechanism could explain findings?
FA 386, poma 35
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.
A patient on heparin therapy develops decreased platelet count.
What autoimmune process could develop?
Should we replace them on warfarin?
FA 405, poma 35
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.
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
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
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
Pt has cystathionine beta synthase deficiency -> increased homocysteine
Homocystinuria.
Homocysteine damages endothelium, which is 1 of Virchow’s Triad.
High homocysteine levels are found in a pt who developed atherosclerosis.
What vitamin could they be deficient in?
FA 108, poma 37
Either Folate or B12 deficiency
both are required for the conversion of homocysteine to methionine
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
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.
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
Factor V Leiden deficiency.
Mutant FV is resistant to degradation by activated Protein C.
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
Prothombin gene mutation 20210A
Thrombin cleaves fibrinogen into fibrin, increasing thrombosis.
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
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)
How does Heparin raise PTT?
Heparin enhances effects of antithrombin.
Antithrombin inhibits activated forms of factors 2, 7, 9, 10, 11, 12, all part of PTT. (FA 386)
Pt presents with petechial rash to chest and hypoxia.
Denies recent bone fracture but did have liposuction surgery last week.
Diagnosis?
Fat emboli. FA 609
Pt presents with pleuritic chest pain, tachycardia, slight fever. Is hypoxic and is in respiratory alkalosis.
What are common lab findings?
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
Caisson Disease
Describe symptoms
Cause
what is decreased in the blood stream?
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
NL platelet count
what is thrombocytopenia
150-400 K/uL
megakaryocytes seen on BM biospy
platelets are being destroyed, so they are trying to make more
immune thrombocytopenic purpura
