Bleeding/Bruising conditions Flashcards
Pathophysiology of DIC
Step 1»_space; blood is exposed to one or more PROcoagulants such as tissue factor, lipopolysaccharides on bacterial products, proteolytic enzymes release for malignant tumors or released from endothelium after trauma
• Conditions the facilitate PROcoagulant activity»_space; hypotension, hypoxemia, acidemia
Step 2»_space;activation of the coagulation cascade, which leads to the production of thrombi consisting of fibrin and platelets
Step 3»_space; amount of thrombin exceeds the supply of the body’s naturally occurring anti-thrombins (protein C, protein S, antithrombin III)
• Uninhibited thrombin activity = unrestricted clot formation
Step 4 »_space; Extensive thrombi formation leads to consumption of the coagulation factors, platelets, and anticoagulant factors
• Consumption of clotting factors = bleeding
Step 5 »_space; Fibrinolysis is activated at the site of thrombi formation »_space; generation of fibrin degradation productions (FDPs)»_space; FDPs in significant amounts in the bloodstream are potent anticoagulants that interfere with clot formation and platelet aggregation »_space; BLEEDING
Final outcome »_space; end-organ damage as a result of reduced perfusion, thrombosis and/or bleeding
Signs/Symptoms of DIC
Bleeding at multiple sites (IVs, drains, incisions)
Bleeding from mucous membranes
Purpura »_space; purpura fulminans = extensive tissue thrombosis with hemorrhagic skin necrosis
Petechiae
Hematoma
Evidence of microvascular thrombosis»_space; AMS, hypoxia, oliguria/hematuria/renal failure, LFT abnormalities, PE, DVT, CVA, cardiac ischemia, hemoptysis
Evidence of macrovascular thrombosis»_space; cyanotic fingers and/or toes
Organ dysfunction 2/2 thrombosis, hemorrhage, or hypoperfusion »_space; renal failure, acute lung injury, neurologic dysfunction
Diagnosis for DIC
Thrombocytopenia
Decreased fibrinogen»_space; acute phase reactant – interpret with caution
Prolonged PT and PTT
Elevated D-dimer
Reduced level of coagulation inhibitors »_space; antithrombin, protein C/S)
Evidence of hemolytic anemia »_space; peripheral smear shows schistocytes/helmet cells due to shearing of RBCs
Evidence of end-organ damage»_space; elevated LDH, elevated Cr, abnormal LFTs
Pathophysiology of APLA syndrome
Presence of specific autoantibodies that are directed against phospholipid-binding proteins»_space; second exposure (smoking, pregnancy, OCPs, malignancy, prolonged immobilization) results in upregulation of Beta2-glycoprotein-1» full-blown syndrome (arterial and venous thromboembolic events)
APLA syndrome diagnosis
- At least one of the following in the setting of vascular thrombosis or pregnancy morbidity (run all three at the same time):
- Anti-cardiolipin antibodies
- Anti-beta-2 glycoprotein-1 antibodies (Russell viper venom time assay test)
- Lupus anticoagulants»_space; can be falsely elevated
- Diagnosis requires two positive antibody test results at least 12 weeks apart»_space; in practice, DO NOT delay treatment waiting on confirmatory test in 12 weeks
- Thrombocytopenia
- Hemolytic anemia
- Prolonger PTT
- Hypocomplementemia
Red flag signs/symptoms for APLA
- Unexplained DVT/PE
- CVA/TIA < 50 years old
- Recurrent thrombosis despite anticoagulation»_space; not caused by noncompliance with medication
- Arterial and venous thrombosis
- Livedo reticularis, Raynaud’s, thrombocytopenia
- Recurrent pregnancy loss
Thrombotic Thrombocytopenia Purpura pathophysiology
ADAMTS13 (vWF cleaving protease) deficiency/defect»_space; vWF multimers remain uncleaved and bound to endothelial cells»_space; large vWF multimers bind to platelets and cause aggregation and RBC shearing»_space; aggregation leads to occlusion of vasculature and microangiopathy
TTP signs and symptoms
Thrombocytopenia »_space; mucocutaneous bleeding – epistasis, bleeding gums, petechiae, purpura, bruising, menorrhagia
Microangiopathic hemolytic anemia »_space; anemia, jaundice, fragmented RBCs, splenomegaly
Neurologic symptoms»_space; HA, visual changes, confusion, seizures, CVA
Fever»_space; rare
Kidney failure or uremia 2/2 microthrombi»_space; uncommon
TTP treatment
Plasmapheresis
Immunosuppression »_space; glucocorticoids and/or Rituximab if no response to plasmapheresis
New drug option»_space; Caplacizumab - monoclonal antibody that targets vWF
ITP pathophysiology
Autoantibodies against platelets, leading to splenic destruction of platelets.
ITP clinical presentation
Often asymptomatic»_space; incidental find on CBC
Petechiae
Ecchymosis
Epistasis
Severe thrombocytopenia»_space; GI/GU bleeding, increased risk for CNS bleed
ITP CBC findings
Isolated thrombocytopenia. Normal WBC, no evidence of anemia
ITP only affects platelets - no other cell lines involved
ITP treatment
Non-life threatening bleeding»_space; observation (85% will spontaneously resolve)
Non-life threatening bleeding + decreased quality of life» prednisone 2-4mg/kg x 5-7 days or IVIG as second line treatment
Refractory ITP»_space; 1st line = thrombopoietin receptor agonist. 2nd line = Rituximab x 4 doses or splenectomy
Hemolytic Uremic Syndrome (HUS) clinical presentation
Thrombocytopenia, microangiopathic hemolytic anemia, renal insufficiency, abdominal pain, bloody diarrhea, fever
Shigatoxin-associated HUS pathophysiology
E. Coli infection»_space; Shiga toxin in blood stream results in endothelial injury»_space; platelet aggregation and local microthrombi formation
atypical HUS pathophysiology
uncontrolled activation of complement on endothelial cells leads to injury and thrombotic microangiopathy
Shigatoxin HUS treatment
Supportive treatment
Dialysis or blood transfusion if needed
atypical HUS treatment
plasmapheresis
Immunosuppression»_space; steroids, Rituximab or Eculizumab (monoclonal antibody that targets complement factor C5)
