hypercoagulable states Flashcards
Calf swelling with edema
you should get an ultrasound to see the clot, and if you start on anticoagulants you risk excessive bleeding
D dimer- fibrin breakdown of a non specific clot, (when you start forming a clot you start breaking down a clot immediateley) sensitive but not specific, sepsis can also cause increased D dimer
If there is a thrombis with positive D dimer, start immediateley with low molecular weight heparin and anti coagulation therapy
Dont start warfarin takes forever, also C S 2 7 9 10, could cause a transient
Bed rest is fatal, tPA has a high side effect, ncreased of bleeding
pulmonary embolism,
things that can contribute to PE are factor 5 leiden, Antiphospholipid antibody syndrome, Protein S deficiency, antithrombin deficiency
Factor 5 leiden is a polymorphism in factor 5 causing resistance to degradation by activated protein C
If there is a factor 5 leiden with PE, you should not give anti coagulants for the whole life, its a weak risk factor for blood clot, physical stuff is much higher for clot, if the patient was younger start and stop
protein c deficiency
Protein C is activated most efficiently by thrombin bound to thrombomodulin
Protein S enhances the effect of activated protein C
Protein C deficiency has an autosomal dominant inheritance pattern
Dissemintated intravascular coagulation causes an acquired protein C deficiency
Decreased protein c is seen in warfarin dependent skin necrosis
Antithrombin deficiency
anti thrombin reacts with both thrombin and activated factor X to inhibit their activity
Diagnosing deep vein thrombosis and pulmonary embolism
differential diagnosis for unilateral edema and erythema includes DVT, superficial thrombosis, cellulitis,, venous insufficiency, lymphedema, and orthopedic injury
For chest pain and dyspnea: broad including cardiac, pulmonary , FI, hepatic, psychiatric and MSK disorders
Use the Wells sore (plus D dimer) and imaging to tell if its a likeley clot
High probability 3, moderate 1-2, low is 0 (Pretty much everything on virchow triangle is on the list
Anticoagulatn drugs
10 stimulates 2, 2 activates fibrinogen to fibrin
ORAL ADMIN
Warfarin: blocks 2 7 9 10
Rivaroxaban, apixaban, edoxaban block 10
Dibigatran blocks 2 a
PARENTERNAL ADMIN
Fondaparinux, enoxaparin, dalteparin (Jane fonda parin’ up)- block 10
Unfractionated heparin blocks 10 and 2
Argatroban bivalirudin- Block 2
Warfarin vs direct oral anticoagulants
Warfarin has a very slow onset of action, many food interatctions drug interactions, predictable drug effects and antidotes
Requires regular monitoring
Inherited resitance to activated protein C (APC) and Factor 5 leiden
most common known inherited thrombophilia, approximately 5-7% of caucasians are heterozygous for the factor 5 leiden mutation
Point mutation in factor 5 gene (ARG–> GLN at amino acid 506 is the initial site of cleavage of factor Va by activated protein C
factor Va is relatively resistant to inactivation
Pregnant woman fatigue malaise and fevere, viral syndrome she takes acetaminophen and rests
altered mental status
Thrombocytopenia in pregnancy is common and also could be due to TTP, ITP, DIC, HUS. vWF does not cause thrombocytopenia but causes bleeding
Thrombotic thrombocytopenic purpura (TTP)
reticulocyte is high, haptoglobin is low, direct antiglobulin test is negative
LDH is high, stool culture is negative
ADAMTS13 activity is 4%
Pentad of TTP: fever, mental status, hemolytic anemia, renal dysfunction, thrombocytopenia
ADAMTS13- a metalloprotease that cleaves high molecular multimer von willebrand factor, that are not as big. so if you have a low ADAMS TS13 you cant chop up the vWF and therefore you get into a high coagulable state
TTP patient treatment
emergency plasma exchange (which has high ADAMSTS13)
large vWF multimers are cleaved by ADAMS TS13
heparin induced thrombocytopenia
ELISA for a platelet should be positive for platelet factor 4 heparin antibody
4Ts: Thrombocytopenia, timing, thrombosis
Moderate thrombocytopenia, suspect if platelet count falls by half, occurs 5-10 days after heparin exposure, associated with thrombotic events (increases risk for thrombosis 20x - 40x) CLOTs including both venous thrombosis and Arterial
treatment, stop heparin therapy, dont start LMWH or warfarin, begin alternative anticoagulation (DTI): argotroban, bivalirudin)
HIT pathophysiology
PF4 binds to surface of platelet following activation, complexes of heparin (GAG) and PF4 molecules form,
IgG binds to the PF4/heparin complex,
IgG/PF4/heparin complex activates via the Fc receptor
Fc stimulation leads to the generation of procoagulant rich microparticles
What hematologic conditions are most commonly associated with petechiae
thrombocytopenia
When a pt has petechiae you should get a CBC with differential , PT/PTT
peripheral blood smear
What causes thrombocytopenia in a young female?
immune mediate thrombocytopenia,
ITP will cause increase megakaryocytes
Splenectomy, thrombopoietin agonists, rituximab (CD20 antagonist)
NO chronic platelet transusions (the is will continue attackit)
