CIS: thrombosis and Hemostasis Flashcards
what is cocktail purpura
when ppl drink gin and tonics and then have petechiae under their eyes with a low platelete count
-the quinine in the tonic causes the platelets to clump and be removed from circulation
What is the most common cause of bleeding
thrombocytopenia
what does the PTT do
asses the intrinsic system
- norm is 25-40 sec
- prolonged in deficiencies of 8,9,11,12
- prolonged in pts on heparin
What is the peripheral smear examination?
evaluates morphology of the formed elements of the blood as well as the numbers of elements present
What could be a cause of thrombocytopenia in a patient?
the medications they’re using
DIC
complication of medical, surgical, and obstetrical situations
- coag systems are actived (ext and intrinsic)
- initial thrombosis, short lived, we don’t see it clinically
- as platelets and clotting factors are depleted, bleeding ensues, which is the major feature of the disease
How to tx DIC
- correction of underlying disorder
- Heparin, not usually used unless over thrombosis occurs
- supportive care, platelet and factor replacement
Thrombotic Throbocytopenic purpura
- thrombocytopenic purpura
- microangiopathic anemia
- fluctuating neurological signs
- renal dysfunction
- febrility
- just add renal failure and it’s HUS
What does the Thrombin time (TT) do?
assesses for abnormalities or deficiency of fibrinogen
ADAMTS13
it cleaves vW factor
- mutation in this gives us the hereditary form of TTP
- Acquired forms come from autoantibodies to ADAMTS13
Tx of TTP
-plasmapheresis: life saving in virtually 100% of cases
What will TTP look like?
- Microangiopathic anemia
- schistocytes, helmets… that is the Waring blender effect
- Pathologic lesion: hyaline thrombi which occlude the capillaries of virtually every organ in the body
vonWillebrand disease
- very large group of related diseases that have their hallmark feature decreased platelet adhesion to the vascular endothelium as mediated by vW factor
- in most cases, the pathologic lesion is decreased or absent production of vWF
tx of vonWillebrand disease
- cryoprecipitate: replaces vWF
- DDAVP- causes release of vWF from endothelium
In what diseases will we see defects in platelet function?
- Uremia: impaired platelet adhesion
- Dysproteinemias: interference with platelet membrane function
- Autoimmune disorders: multiple abnormalities
What diseases will give us hemorrhage related to factor deficiency?
- Hemophila A and B
- vW disease
- Vit K dependent factors
- usually a prolonged coagulation times (PT,PTT)
Hemophilia A
- X linked recessive trait characterized by a deficiency of factor 8
- risk of bleeding corresponds to degree of deficiency
- mild (6-25%), moderate (1-5%), or severe (<1%)
presentation of Hemophilia A?
- easy bleeding and bruisability
- hematomas from bleeding into soft tissues and muscles
- hemarthroses… frequent
- patients are at significantly increased risk for bleeding during and after surgery
Hemophilia B
decrease in factor 9
- looks like hemophilia A
- tx with factor 9
characteristics of Deficiency of Vit K dependent factors
- bleeding/hemorrhage
- prolonged PT
- Deficiency of factors 2,7,9,10 ptn C and S
Hereditary Hemorrhagic Telangiectasia
aka: Osler-Weber-Rendu syndrome
- the only endothelial syndrome associated with hemostatic complications
- caused by thinning of vessel walls with telangiectatic formations, arteriovenous malformations, and aneurysmal dilatations throughout the body
Hereditary hemorrhagic telangiectasia genetics
- Autosomal dominant inheritance
- Defect in gene coding for endoglin (CD105) a membrane glycoprotein strongly expressed on endothelial cells
- located on chromosome 9
clinical features of hereditary hemorrhagiv telangiectasia
- telangiectasias: gradually appear throughout life located in skin, mucous membranes, and visceral tissues
- Bleeding: to mild or inapparent trauma; epistaxis is the most frequent symptom (80%)
Course and tx of HHT?
- usually benign , recurrent bleeds frequent but death from exanguination is rare
- surgery and laser photoblation of telangiectasias of value but care must be used in selecting site
Thrombotic disorders
- antithrombin III deficiency
- Ptn C and S deficiency
- Factor V leiden syndrome
- Prothrombin 20210
- Antiphospholipid Syndrome
- Superficial venous thrombosis
ATIII deficiency presentation?
- recurrent lower extremity thrombophlebitis and DVT, venous insufficiency, and chronic leg ulcers
- significantly incrased risk for DVT in pregnancy i
- diagnosis: demonstration of diminished levels of ATIII in serum (<50% of normal activity
normal PT
10-15 sec
What organ produces clotting factors
the liver
- so a cirrhotic patient will have a coagulopathy
- give them fresh frozen plasma because that has clotting factors in it!
Fondaparinux
its a direct thrombin inhibitor
-used to minimize risk of post op DVT
Where do Ptn C and Ptn S work?
factor 5
Tx of ATIII deficiency
prophylactic tx with anticoagulants
- pts with DVT need heparin
- ATIII replacement therapy for ppl who dont respond to heparin
What does Ptn C do
inactivates factors V and VIII
What does Ptn S do?
cofactor for Ptn C
-kinda supercharges it and makes it work better
What is the most common cause of hypercoagulable state from deficiency of ptns C and S?
initiation of warfarin therapy
-C and S are depleted prior to the other factors, resulting in a temporary increase in coagulability
Factor 5 Leiden
- abnormality of factor V at binding site for activated Ptn C
- risk for thromboembolism
Tx of Factor V leiden
- no prior episodes: monitor; DVT prophylaxis and risk reduction
- Prior episodes: consider lifelong anticoagulation
Prothrombin 20210
- G-A mutation resulting in increased activity for prothrombin and inability to de-activate prothrombin
- risk of thrombosis very high…. combined with factor V leiden may account for most cases of hereditary thrmobophilia
Tx of prothrombin 20210
along the same guidelines as factor V leiden
Antiphospholipid syndrome
-circulating antibodies to phospholipid….
poorly understood
associated features of Antiphospholipid syndrome
thromboembolic phenomena
- miscarriage
- thrombocytopenia
- cerebral ischemia and recurrent stroke
- UBO: unidentified bright objects on MRI scan
diagnosis of Antiphospholipid syndrome
3 tests:
- a prolonged phospholipid-dependent coagulation test (PTT)
- lack of correction in mixing studies using normal plasma
- neutralization of inhibitor with excess phospholipid
What is DRVVT
Dilute russell viper venom time: may be more specific than PTT-related test
Tx of antiphospholipid syndrome
- if no thromboembolic disease hx, no benefit for anticoagulation
- for those with a history: lifelong anticoagulation…. don’t base on a single test! Multiple positive tests over a 3-12 month period are required to make diagnosis
- anticoagulation during pregnancy may be accomplished by SC heparin
- Hydroxychoroquine-
What was happening in that case with the lady with a DVT and taking oral contraceptives?
her bro had Factor 5 leiden… so she was a heterozygote
-that superimposed on the factor 5 leiden risk gave her a hypercoagulable state
