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
