Freeman Flashcards
What is the incidence of Factor 5 Leiden? HOw does this affect your risk if you are heterozygous or homozygous for it?
hyper coagulability risk
Incidence: 3-8%
Hetero: 8X risk
Homo: 20X risk
What are some of the things that affect your mechanical flow dynamics?
prior sites of thrombus compression due to obesity chemical *nicotine *vasoconstricting agents
What are some modifiable risk factors for coagulation?
Obesity
Sedentary life-style
Travel
OCP
Pregnancy
Surgery
*elective, particularly
ortho
Smoking
Prior DVTWhat are som unmodifiable risk factors for coagulation?
Factor V Leiden
Prothrombin Gene Mutation
Malignancy
Surgery
*emergent
Chronic Illness
Lupus AnticoagulantWhat is the treatment for acute thrombogenesis?
Warfarin + Heparin
Heparin for 7-10 days
Which factors are Vit K dependent?
2, 7, 9, 10
Proteins C& S
**Vit K carboxylates the N terminus of these factors to activate
What is the half life of Factor X?
48 H
Note: this is a coagulant.
What is the half life of Protein C?
6 hours
Note: this is an anticoagulant
Why is it that you have to treat patients struggling with coagulation with heparin for a full 7-10 days?
b/c the factors that are alive & active take some time to die.
4-5 half lives.
This equals out to 7-10 days. Otherwise: just get a blood clot a few days later.
What affects the course of Warfarin?
based on the etiology of the thrombogenic event
When do you sometimes see lupus anticoagulants?
may be seen at the time of acute thrombotic events (acute phase reactants)
How is a lupus anticoagulant identified in lab? In vitro & in vivo?
In vitro: prolongs PTT
in vivo: procoagulant.
When a patient is taking both heparin & warfarin…when should the warfarin be instituted?
it can be initiated at the same time as heparin
66yo male admitted to Med Center w/hypotension, tachycardia, & fever.
W/U reveals gram(+) septicemia 2/2 staph aureus. Echocardiogram reveals mass in ‘upper’ R-ventricle. Nurses report patient ‘oozing’ from all iv sites.
EXAM: b/L foot amputations
No obvious source of skin
breakdown/infections
LABS: PT 13.3 secs (nl: 11-12.2 secs)
1:1 mixing study: PT normalizes
PMHx: DMII; no h/o cardiac dz.
D/C’ed 3 weeks earlier for gram(+) sepsis @ that time.
What’s going on?
the normalizing with the mixing study shows that this person probably has a factor deficiency
seems to be suffering from heparin inducted thrombocytopenia
**seems to have endocarditis after a staph aureus septicemia that induced DIC
Same pt
On admit, platelet count 175K (Nl: 150-400K)
Started on LMWH (Lovenox) prophylactically on admit; next day, platelets are 45K.
The ICU team requests Heme consult regarding recommendations for anticoagulant agent of choice; they suspect HIT. Cardiology suggests treatment of thrombus.
Your recommendations?
What should be done for this patient?
stop the heparin!
treat the endocarditis
DIC will go away…
Explain what happens in type I HIT.
- *Modest, transient decrease in platelets 2/2 heparin-induced platelet agglutination.
- *Self-limited; plt counts can return to normal while heparin is continued.
Explain what happens in Type II HIT.
A drug-induced, immune-mediated response 2/2 abs directed against heparin-plt factor 4 complete that results in a 50% or greater drop in platelet counts
**Severe thrombocytopenia w/bleeding is rare!
HIT is less likely with which type of heparin? When is HIT usu seen?
usu seen after major surgery where large volumes of heparin are required
less likely with low molecular weight heparin
What Should be considered in all recently hospitalized patients returning w/acute thrombosis w/in 1-2 weeks of their hospital stay?
HIT
shows thrombocytopenia & thrombosis!
What is the testing done for HIT? What is the treatment?
Testing: radiolabeled platelet-serotonin release assay
Rx: direct thrombin inhibitors
Why is there both thrombosis & thrombocytopenia in HIT?
blood clots being made
consumption of platelets
also autoimmune destruction of heparin-platelet 4 complex
How do you measure the effectiveness of 10a inhibitors?
measure 10a
measure D-dimer
What is the pathophysiology of DIC?
Widespread activation of the clotting cascade causing a consumption of clotting factors and platelets w/resultant bleeding.
Microvascular compromise 2/2 to thrombin formation results in tissue ischemia w/resultant end-organ damage, particularly of liver & kidneys.
DIC is triggered by diseases that promote the expression of tissue factor (transmembrane glycoprotein). Give some examples.
- Gram(-) septicemia
- damaged cerebral tissue
- APL (promyelocytic leukemia) awa other liquid/solid malignancies.
- Placental tissue from obstetric catastrophes
- Snake venoms
- Acute hemolytic transfusion rxns
- Hypotension from any cause can result in endothelial cell damage(CABG, etc.
- Massive Tissue Injury: trauma;burns; hypothermia
What is the cause of activation of the coagulation cascade in DIC?
Endotoxin
IL-1
TNF alpha
**tissue factor is released in response to the presence of these cytokines
What are the characteristic lab findings in patients with DIC?
Prolonged PT/PTT or both.
Thrombocytopenia
Decreased fibrinogen levels
Increased D-dimer
What are some disorders of coagulation that can lead to bleeding?
platelet disorders
factor disorders
What are some disorders of organ systems that can lead to bleeding?
renal failure
liver failure
hematopoietic
coronary artery issues
What are some drugs that could cause bleeding?
GP IIb/IIIa inhibitors(Plavix) COX I inhibitors(ASA) Heparin Coumarins OTC *Ginko *Ginseng
What is the appropriate drug to treat bleeding due to renal failure? What does it do?
DDAVP
releases factor 8 from weibel palace bodies in endothelial cells of blood vessels
What are the possible causes of a prolonged PT?
malnutrition
liver disease (due to decreased synthesis of Vit K factors)
coumadin
What are the possible causes of a prolonged PTT?
lupus anticoagulant/acquired factor inhibitors
vWD
Factor 8/9 deficiency or inhibitor
heparin
If a mixing study is not corrective…what are you thinking?
there is an inhibitor present
**next step: check specific factor assays
If a mixing study is corrective…what are you thinking?
deficiency of a factor
perform a factor assay
DDAVP is contraindicated in which condition ?
type II von wilebrand’s disease
What’s the deal with factor 8?
there are 2 different molecules
one is for vwd & binds to endothelial cells
another is used for hemophilia treatment & has a different mechanism & is a procoagulant
Can a baby with possible vwd have a circumcision?
yes
b/c some of the good factor 8 from the mom will have crossed the placenta
the babies shouldn’t bleed for a few months
What are the different ways that you can get vwd?
Inherited; autosomal dominant Type 1: Quantitative deficiency Type 2: Qualitative deficiency Type 3: Total deficiency Acquired *lymphoproliferativd disorders: can create antibodies to factor 8 *Monoclonal gammopathies *MPS, particularly ET: ET—essential thrombocytosis *Mechanical (Heidi’s Syndrome)
How is vwd inherited? WHat does it look like clinically?
aut dom
mucosal oozing after surgery or trauma
How is hemophilia inherited? What does it look like clinically?
x-linked
clinically spontaneous hemarthroses
Hemophilia B is also known as what?
Factor 9 problem
Christmas!
Patient presents w/symptomatic AS. During w/u, he is found to have microcytic anemia. FOBT is (+). PTT is prolonged @ 12.9(nl 11.7); 1:1 mixing study corrects PTT to 10.8. EGD (-) but colonoscopy reveals (3) polyps in R-colon. Capsule endoscopy reveals scattered, slightly bleeding av-malformations in ileum. To Rx the condition, you order…..
- DDAVP intranasal spray during acute bleeding episodes.
- Factor VIII replacement during acute bleeding episodes.
- R-hemicolectomy
- Aortic Valve Replacement
- Partial small bowel resection.
- Amicar 1 gm q6HRs to seal clots @ site of small vessel bleeds (anti-fibrinolytic).
Aortic Valve Replacement
What is Heyde’s Syndrome?
A syndrome caused by aortic valve stenosis resulting in GI bleeding @ sites of colonic angiodysplasia w/exaggeration of bleeding 2/2 mechanical destruction of ultra-large von Willebrand factor molecules(acquired vWD).
A 36 year old male presents not the emergency department with a 36 hour history of headache and intermittent episodes of aphasia. He has no significant past medical history and takes no medications. Other symptoms include intermittent low-grade fevers with temperatures to 38.5°C. On examination, he has mild left sided weakness without other abnormalities. Initial laboratory examination reveal moderate renal insufficiency, a hemoglobin of 9.2 g/dl, and a platelet count of 42 x 109/L. Coagulation tests are normal. Examination of the peripheral blood smear reveal frequent red cell fragments. The lactate dehydrogenase level is approximately 4 times the upper limit of normal.
Which of the following is the most likely cause of this patient’s disorder?
Disseminated intravascular coagulation
Drug-associated toxic reaction
A hereditary form of thrombotic thrombocytopenic purpura
An acquired antibody-mediated microangiopathic disorder
C. TTP
disorder can be due to autoantibody against ADAMTS13, involved in vwfactor processing.
microvascular fibrin deposition & thrombocytopenia associated with hemolysis
treat with plasmapheresis
What is quintad in TTP?
Fever MSΔ’s Renal insufficiency Microangiopathic HA Thrombocytopenia
What are the lab abnormalities seen in TTP?
Anemia/thrombocytopenia
Very Raised LDH
Raised serum creatinine
Peripheral Smear: schistocytes
What are some possible causes of acquired ADAMTS-13 antibodies?
E coli idiopathic autoimmune disease drug associated bloody diarrhea prodrome pregancy, postpartum hematopoietic cell transplantation
