Bleeding Disorders Flashcards
What is hemostasis?
process of clot formation and subsequent breakdown
- balance between clotting and fibrinolysis
- excess clotting = thrombosis
- excess fibrinolysis = hemorrhage
What are the 4 steps in hemostasis?
- endothelial injury
- primary hemostasis - platelets and vWF form platelet plug
- secondary hemostasis - clotting factors form fibrin clot
- fibrinolysis once injury is no longer present
How does endothelial injury start off hemostasis?
injury to vascular endothelium results in localized vasoconstriction to reduce blood loss and tissue factor exposure to blood, initiating coagulation
What are the 4 steps to primary hemostasis?
- vWF at the site of endothelial injury and collagen exposr=ure causes platelet adhesion
- platelets undergo changes in their shape (activate!)
- platelets release granules of ADP and TxA2 to recruit more platelets
- more platelets aggregate and form the hemostatic plug (linked together with fibrinogen and vWF)
What are the 2 pathways of blood coagulation during secondary hemostasis? What coagulation factors take part in each? What tests evaluate each?
EXTRINSIC - factor VII activated by tissue factor release with blood exposure; PT
INTRINSIC - factors XII, XI, IX, VIII activated by direct collagen contact; PTT
What are the steps in the intrinsic, extrinsic, and common pathways of blood coagulation?
INTRINSIC - rollback special ($12 —> $11.98)
EXTRINSIC - 7 + 3 (TF) = 10
COMMON - 10/5 = 2
What does secondary hemostasis require? How does it occur?
clotting factors and fibrinogen produced by the liver
- prothrombin is cleaved into thrombin
- thrombin converts fibrinogen into fibrin
- factor XIII is activated and crosslinks fibrin to stabilize the initial blood clot
What 2 things occur during fibrinolysis?
- plasminogen is converted into plasmin by tissue plasminogen activator (t-PA)
- fibrin monomer and x-linked fibrin are broken down into degradation products by plasmin, resulting in the production of FDPs and D-dimers and removal of the fibrin plug
(FDPs and D-dimers can be measured to analyze abnormal clot formation and fibrinolysis)
What coagulopathies are associated with primary and secondary hemostasis?
PRIMARY - thrombocytopenia, thrombocytopathia, endothelial disease
SECONDARY - congenital/acquired coagulopathies
What are 6 common presentations in patients with bleeding disorders?
- black stool (melena) - GI bleeding
- owner or groomer notices petechia and ecchymosis
- bloody urine
- known/possible ingestion of vitamin K rodenticides
- sudden collapse
- hemoabdomen
What clinical signs are associated with primary hemostasis?
- petechia, ecchymosis
- mucosal hemorrage
- epistaxis
- urinary hemorrhage
- melena
- hematemesis
What clinical signs are associated with secondary hemostasis?
- ecchymosis
- hemarthrosis
- body cavity hemorrhage
- melena
- hematemesis
What should be avoided in patients with high probability of hemorrhage when trying to diagnose causes of coagulopathies?
jugular vein sampling
What testing is most commonly used for diagnosing primary vs secondary hemostasis?
PRIMARY - platelet counts, buccal mucosal bleeding times (should be around 4 mins), vWF concentration
SECONDARY - prothrombin time (extrinsic, common), partial thromboplastin time (intrinsic, common), D-dime (DIC, hypercoagulability)
- park trucks (PT) outside
- poker table tournament (PTT) inside
What are the most common tests for analyzing platelets taking part in primary hemostasis?
platelet coount - thrombocytopenia most common, does NOT assess platelet function
buccal mucosal bleeding time - assess function of platelets and endothelium —> should take about 4 mins
What are the major tests for secondary hemostasis?
prothrombin time (PT) = extrinsic, common
partial thromboplastin time (PTT) = intrinsic, common
What are the 2 major tests of overall hemostasis?
- fibrin degradation products (FDP) - increased due to fibrinolysis or excessive coagulation
- D-dimer - more accurate than FDP
When are clinical signs of thrombocytopenia seen? What signs are characteristic?
bleeding = <50 k/uL
(<30 k/uL)
- petechia
- mucosal hemorrhage
- epistaxis
- urinary hemorrhage
- melena
What is thrombocytopenia? What must also be done fora diagnosis? Why?
decreased platelet numbers
confirmation with a manual blood smear
pseudothrombocytopenia commonly seen with platelet clumping (cats!) and congenital macrothrombocytopenia where the machine do not recognize these platelets
What is congenital macrothombocytopenia? What breeds are predisposed?
inherited abnormality in platelet formation with a count ranging from 50000-100000/uL with many larger circulating platelets —> no bleeding tendencies
- Cavalier King Charles Spaniels
- Norfolk Terriers
- Cairn Terriers
What are the 4 major causes of thrombocytopenia?
- destruction - immune-mediated, infection, vaccination
- consumption - DIC, neoplasia, vasculitis, hemorrhage
- sequestration - hypersplenism
- decreased production - immune-mediated, marrow neoplasia, Ehrlichiosis, FeLV, myelodysplasia, myelofibrosis
What is idiopathic immune-mediated thrombocytopenia (IMTP)? What breeds are predisposed? What clinical signs are associated?
abnormal immune response directed against platelets +/- megakaryocytes
- Cocker Spaniels
- Old English Sheepdog
- Poodle
spontaneous hemorrhage without other signs of illness
What are the 3 most common laboratory findings associated with IMTP? What additional finding is less common?
- severe thrombocytopenia (0-20000/uL)
- regenerative anemia (blood loss)
- hemorrhage* - hypoalbuminemia, hypoglobulinemia, elevated BUN
hemolysis (Evan’s syndrome) - hyperbilirubinemia, spherocytosis, RBC agglutination
What is the most common cause of IMTP? What are 4 other possible causes?
PRIMARY = idiopathic, must rule out everything else
SECONDARY
- drugs - Cephalosporins, Penicillins, Sulfonamides
- vaccination
- infection - Rickettsial (Ehrlichiosis, Anaplasmosis, RMSF, Borreliosis), FeLV, focal infections
- neoplasia - lymphoma
What diagnostics are recommended for IMTP?
- minimum database (CBC/Chem, UA) - r/o UTI, assess organ function
- blood smear - confirmation, r/o hemolysis (Evan’s), evaluate for infection or neoplasoa
- thoracic rads / abdominal ultrasound - evaluate for neoplasia or focal infection
- infectious disease testing - 4DX Snap or SNAP FIV/FeLV +/- PCR and serology panels based on suspicion for Rickettsial disease
What are the 3 major treatment principles for IMTP? What is the initial goal?
- identify and treat any underlying causes
- suppress the abnormal immune response
- maintain tissue perfusion and oxygenation
increase platelet count above the threshold for spontaneous hemorrhage (30000/uL)
What immunosuppressive is recommended for IMTP treatment? What 4 can be added on if there is no response?
Prednisone - effective by itself in most cases
- Azathioprine
- Mycophenolate
- Cyclosporine
- Leflunomide
What 2 adjuvant treatments or IMTP are recommended?
aid immune system temporarily
- Vincristine
- IVIg - Ig blocks Fc receptors on macrophages to block platelet consumption
What treatment is recommended for Rickettsial infections that may trigger IMTP? How is it started?
Doxycycline - Ehrlichia, Anaplasma, Borrelia, RMSF
start while waiting for infectious disease results (or if testing is not possible) and continue for 28 days