Bleeding Disorders Flashcards
(34 cards)
1
Q
Heredity/acquired bleeding disorders
A
- FH, males/females, complications post circumcision
- The baby’s liver hasn’t quite caught up with all of the clotting factors, etc. babies tend to bleed more
2
Q
medications for bleeding disorders
A
-ASA, Coumadin (Are they taking an aspirin a day? Did they just come out of the hospital where they were on heparin the entire time)
3
Q
tendency for bleeding disorders
A
-Epistaxis, bruising, ecchymoses, bleeding p venipuncture, gums p brushing (Most common cause of nose bleeds – digital trauma, Ecchymoses are raccoon eyes)
4
Q
hereditary hemorrhagic telangectasias
A
- Osler, Weber, Rendu
- AD inheritance
- Vascular malformations
- Skin/mucosal malformations on tongue, hands/fingers, nose, lips, conjunctiva
- Also brain and lungs
- Pathophysiology: defects of TGF beta-1 effect formation of connective tissue necessary for BV formation -> AVM
5
Q
Ehler-Danlos syndromes
A
- All effect collagen structure (28 genes, 19 types)
- Easy bruising, hyperelasticity of skin, hypermobility of joints, weakness of tissues (Can develop bony growth that are painful)
- Vascular type (type IV) – joint or blood vessel ruptures 20-40 yo
- 1:5-10,000
6
Q
Marfan Syndrome
A
- Genetic d/o of connective tissue
- Fibrillin-1 (Chr 15)
- Fibrillin 1 binds TGF-beta causing local inflammatory effects damaging aorta, valves
7
Q
features of platelet disorders
A
- Spontaneous bleeding
- Prolonged BT
- Normal PT
- Normal PTT
- Low count
8
Q
Thrombocytopenia
A
- you have too few thrombocytes (platelets)
- Decreased production: aplastic anemia (pancytopenia) – breakdown in bone marrow where you stop making megakaryocytes so no more platelets; Marrow infiltration (leukemia) – makes the marrow not produce adequate numbers; Ineffective thrombopoiesis (B12/folate); Increased destruction – widespread clotting because you’re clotting everwhere; Infection (HIV); Consumption (DIC)
9
Q
Drug effects
A
o Quinidine o Sulfa o PCN o Heparin o Thiazides
10
Q
ITP
A
- Idiopathic thrombocytopenic purpura
- Female 20-40, possibly assoc with SLE
- IgG vs GPIIb/IIIa surface receptors
- Removal of targeted platelet by spleen
- MCC thrombocytopenia in children
- No splenomegaly
- Must examine marrow for increased megakaryocytes
- Tx: Steroids, splenectomy (Steroids because its autoimmune and splenectomy because that’s the defective agent)
11
Q
TTP
A
- thrombocytopenic purpura
- Primarily Women
- Pentad: Thrombocytopenia, Microangiopathic anemia – damage to the small vessels – chews up red blood cells faster than they should and so they are anemic, Neurologic changes, Renal failure, Fever, Schistocytes are damaged RBCs that are indirect evidence of TTP
12
Q
pathophysiology and tx of TTP
A
Pathophysiology:
- Extensive microscopic clotting in small blood vessels by failure to cleave vWF polymers (enzyme ADAMTS13). Shear stress on RBC -> hemolysis.
- Darkening of urine from hemolytic anemia
- Small clots lead to widespread areas of ischemia
- N/V from gut ischemia – because they are clotting everywhere
- Causes shear stress on vessel walls that leads to leaking of blood
Tx:
-Plasmapheresis – get all the gunk out
13
Q
heparin induced thrombocytopenia
A
- Several days of heparin or LMWH tx
- IgG mediated complexes destroy platelets
- Unexplained platelet loss or sudden bleeding
- Withdraw agents, get assay for previous hx
14
Q
hemolytic uremic syndrome
A
- Infants and young children
- Similar to TTP without neuro and more severe renal disease often progressing to ARF.
- May be associated with E coli toxins
- Chemotherapeutic agents
- Diarrhea and URI are MC inciting factors
- Tx: plasmapheresis
- Use of antimotility agents in D may increase risk
- Immune complexes implicated
15
Q
coagulation disorders
A
Factor Deficiency
- Production
- Inhibition
- Consumption
- Liver disease
16
Q
factor VIII deficiency
A
- Hemophilia A (Classic)
- Required for activation of factor X by intrinsic pathway
- Liver synthesis
- Bound to subendothelium by vWF
17
Q
hemophilia A
A
- Genetic Defect, X-linked
- In up to 30% of pts, spontaneous mutation
- 10% have normal factor levels, but inhibited by autoantibodies
- 1:5,000 males in US
18
Q
presentation of hemophilia A
A
- Late rebleeding – they have a hard time forming platelet plugs
- Hemarthroses – they bleed into joints
- Bruising
- Massive hemorrhage
19
Q
laboratory findings for hemophilia A
A
- BT normal – tests for platelet disfunction
- Platelets normal
- PT normal (test for extrinsic pathway)
- Prolonged aPTT (this is the test for intrinsic pathway)– corrected by mixing with normal plasma containing factor
- Factor VIII assay decreased
20
Q
treatment for hemophilia A
A
- Factor replacement
- Desmopressin Acetate for smaller bleeds (Sounds like vasopressin and it constricts blood vessels)
21
Q
Christmas factor - IX
A
- Factor IX (Hemophilia B)
- Differentiated from Hemophilia A by factor assay
22
Q
von willebrand disease
A
- Problem with Von Willebrand factor (People who get their wisdom teeth out and keep oozing blood, women with really long periods)
- Presentation with spontaneous bleeding from mucus membranes, oozing after procedure, menorrhagia. (Hemophilia pt bleeds like crazy, this is the difference)
- AD and AR forms
- This is all about failure of platelets to form a platelet plug -> they can’t stick together well!!
- Very common! 1/100
23
Q
laboratory w/u of vWF
A
- Prolonged BT – cant form a platelet plug and seal the hole
- Prolonged aPTT, normal PT
- Low vWF levels
- Possible low level of factor VIII d/t loss of stabilizing influence of vWF (vWF allows factor 8 to survive longer and stick around longer, But sometimes when you get a blood level for someone, their factor 8 can be low so you don’t know which one is the culprit)
24
Q
ristocetin aggregation test
A
- Antibiotic facilitating binding of VIII:vWF complexes to GPIb receptor. Absence of aggregation predicts low VIII, vWF or receptor deficiency.
- Gold standard USED to be the ristocetin aggregation test -> if platelets didn’t aggregate, you could narrow down to factor 8 or vWF.
25
DIC
- disseminated intravascular coagulation
- Systemic, intravascular thrombo-hemorrhagic disorder
- Formation of thrombi widespread
- Consumption of platelets and factors, secondary activation of fibrinolysis
- Secondary manifestation
- They are clotting and breaking down clots all the time
- Often very quickly FATAL
26
disorders associated with DIC
- Abruptio placenta
- Infection (meningococcemia, GN sepsis
- Metastatic CA
- Burns
- Hemolytic transfusion reactions
27
pathophysiology of DIC
- Activation of coagulation and fibrinolytic systems -> simultaneously forming and breaking down clots
- Release of tissue factor (thromboplastin) activates extrinsic pathway (placenta, leukemic cells, endotoxins)
- Widespread endothelial injury activates intrinsic pathway (Once you kick off that clotting, the endothelium activates everything)
- Factor XII activates kinins – vasodilation (shock) – also activates fibrinolysis (D Dimers formed) (TEST OF CHOICE FOR DIC!! (D dimer))
- Result = bleeding + thrombosis
28
presentation of DIC
- Ill or OB patient
- Oozing of blood from wounds
- Subcutaneous bleeds
- Microthrombi in kidneys -> RF
- Microinfacrtion of heart
- ARDS
- Intracerebral bleeds/CVA
- Microangiopathic hemolytic anemia
- Anterior pituitary involvement (Sheehan Syndrome) – postpartum pituitary necrosis
29
laboratory w/u of DIC
- Platelets low – because they’re clotting everywhere!
- PT/aPTT prolonged – because they’re clotting everywhere so they’re burning up factors
- D-Dimer diagnostic (When you start to break down fibrin (from a clot), the breakdown products are known as D dimers)
30
hemolytic transfusion reaction
- Autoimmune pt reacts to donor antigens
- Usually ABO incompatibility
- Hemoglobinemia, hemoglobinuria, DIC, anaphylaxis
- Massive transfusions dangerous (entire volume < 24 hr, 10u in 12 hr) (Much greater risk of a hemolytic reaction)
31
medications for clotting disorders
- Decrease clotting (Heparin, LMWH, warfarin, antiplatelets, thrombolytics)
- Increase clotting (Vit K, FFP, factor replacement, antifibrinolytics, desmopressin)
- Can give: Blood (PRBC), FFP, platelets, cell saver (salvage), pre-op banking
32
heparin
- Discovered 1916 in dog liver by JH med student
- Short t1/2, preg C
- Factors 2, 9, 10, 11, antithrombin 3
- aPTT
- LMWH – reliable dose-dependent effects, 6-12hr t1/2, injectable
- 50% reduction in DVT rates with post-op use
- Protamine sulfate reverses
- Protamine goes with heparin, vit K goes with warfarin
33
warfin (coumadin)
- 1921 – only oral anticoagulant
- Vit k analog inhibits metabolism of vit K dependent factors
- Reversed by administration of Vit K!
34
ASA
- Acetylsalicylic acid
- COX 1 and 2 inhibitor
- Inhibits prostaglandin and thromboxane production
- Blocking thromboxane A2 production prevents platelet aggregation
