Thrombotic Thrombocytopenic Purpura (TTP)

Pathophysiology:

• Insufficient ADAMTS-13 activity allows vWF multimers to accumulate in microcirculation which leads to platelet aggregation/thrombocytopenia and hemolysis of RBCs.

Risk Factors:

• Congenitally deficient ADAMTS-13 activity AND:
  • Pregnancy OR
  • Infection OR
  • Inflammation OR
  • Medication use (quinolones, ticlopidine, clopidogrel)

Clinical Features:

• Microangiopathic Hemolytic Anemia
• Thrombocytopenia
• Fever
• Renal pathology
• CNS abnormalities (headache, seizure, altered mental status, CVA, coma)

TTP pentad mnemonic = FAT RN

• Fever, Anemia, Thrombocytopenia, Renal, Neuro Symptoms

Workup:

• CBC with peripheral smear (anemia, microspherocytes, thrombocytopenia are suggestive findings)
  • Microangiopathic hemolytic anemia produces schistocytes
• LDH (elevated)
• Haptoglobin (decreased)
• Reticulocyte count (appropriate)
• UA (hemoglobinuria)
• Creatinine (possibly elevated)
• LFT’s (increased bilirubin)
• PT/PTT/INR (normal; differentiates from DIC)
• Urine pregnancy (significant association between pregnancy and TTP)

Management:

• Heme Onc Consultation, Plasma exchange, FFP Transfusion, Glucocorticoids

Aplastic Anemia

Etiology:

• Absence or decreased number of hematopoietic precursor cells → pancytopenia (anemia, thrombocytopenia, neutropenia)
  • Drug induced, viral infection, autoimmune, congenital

Presentation:

• Anemia (weakness, fatigue, dyspnea), Thrombocytopenia (mucosal bleeding, petechiae, ecchymosis), Neutropenia (recurrent infection, fever)

Workup:

• CBC (pancytopenia), CMP, Reticulocyte Count (reduced or absent), peripheral smear, LDH, Haptoglobin, consider viral serologies

Management:

• Heme Onc consultation for all new cases, especially if severe
• Transfuse PRBS/platelets as needed for severe anemia/thrombocytopenia

Angioedema

Etiologies:

• Mast cell activation/Histamine-mediated
  • Allergic angioedema: IgE-mediated type I hypersensitivity
• Bradykinin-mediated

• Hereditary angioedema: Congenital or acquired loss of C1 esterase inhibitor
• Due to C1 esterase inhibitor deficiency
• Leads to unregulated activity of vasoactive mediators (bradykinin) associated with complement pathway
• Autosomal dominant
• ACE-Inhibitor induced angioedema: ACE-I adverse reaction from excessive bradykinin
• Unknown/idiopathic

Differentials: Anaphylaxis, Contact dermatitis, cellulitis, tonsillitis/uvulitis, PTA, retropharyngeal infection

Clinical features:

• Affects loose connective tissue (face/lips/throat, extremities, genitalia, bowel wall)
• Not gravitationally dependent
• Onset minutes to hours, Resolution hours to days

Workup:

• Testing not always needed, UTD recommends CBC, CMP, ESR/CRP, C4 level (c4 level +/- c1 inhibitor antigen testing used for future diagnosis, not part of ED management)
• Imaging not typically needed unless concern for concurrent dx (i.e. infection, abscess)

Management:

• General: Epi, Glucagon, TXA, FFP
• Hereditary/C1 acquired deficiency: Purified C1 inhibitor, kallikrein inhibitor, bradykinin b2, orally available Kallikrein
• FFP- can be used if other aren’t available.

Intubation strategies:

• Anticipate difficult airway, have backup available if possible
• Be prepared for being unable to oxygenate and ventilate, be ready to perform cric
• Be as gentle as possible- tissue is friable, irritation will cause more swelling.
• Consider intubation early-angioedema can surprise you and progress very rapidly.
• Consider intubation very early in post-TNKase cases, as cric could be devastating
• Digital (tactile) intubation strategy: Use the non-dominant index/middle fingers to palpate the epiglottis, directing a boujie or ETT into the trachea.

Dispo:

• No consensus on timing needed for obs. If stable need to be observed until signs of improvement. Most non-allergic angioedema does not fluctuate in severity.
• Consider admission: If partly allergic picture, high risk body part (airway), poor social situation
• Consider transfer: Low resource facilities, no advanced airway clinician except you, consider airway compromise en route (sometimes early intubation is the safest option prior to transfer)

Anticoag/Antiplatelet Reversal