Interactive Medical Cases

A 43-year-old woman presented to the emergency department with confusion and gingival bleeding. She did not have a prior medical history and did not use any medications.

A few days earlier, she complained of flu-like symptoms. Her husband had noticed that for the past 24 hours she was somewhat confused and before arriving at the emergency department she had one episode of generalized tonic-clonic seizure.

Her temperature was 37 °C, heart rate 123 bpm, blood pressure 126/76 mm/hg, respiratory rate 26 breaths per minute, and oxygen saturation 96 % while breathing room air. The patient was disoriented in time, place and person, but showed no focal neurological signs. There was coagulated blood in the nostrils and oral cavity, and petechiae on the lower extremities. Examination of heart, lungs and abdomen was normal and there was no blood on the rectal digital examination.

The initial laboratory results showed a WBC of 8300/mm³ (N 4-10 000) with a normal differential count, Haemoglobin 5.3 g/dL (N 12-14), MCV 90 fL (N 80-100), reticulocytes of 200 000/mm³, and a platelet count of 21,000/mm³ (N 150 -400 000 /mm3). There were normal coagulation tests (PT 11 sec (N 11-12.5), aPTT 29 sec (N 25-36), fibrinogen 150 mg/dL (N 130-330). Serum electrolytes and renal function were normal. Liver tests showed elevated LDH and bilirubin levels 3.2 mg/dL (N <1.2), mostly indirect/free, AST and ALT were normal. C-reactive protein:  6 mg/L (N < 5 mg/L)

A Covid test and Beta-HCG test were negative.

================================

What is the most appropriate first step for this patient?

Feedback

The first step is to perform brain imaging and search for hemorrhagic complications because of thrombocytopenia and one episode of a seizure.

Petechiae and thrombocytopenia could be a sign of purpura fulminans that may follow acute sepsis caused most often by Neisseria meningitidis or Streptococcus pneumoniae. The patient doesn’t have a fever nor raised inflammatory biomarkers and as such IV antibiotics are not mandatory yet.

Lumbar puncture for liquor examination is contraindicated if increased intracranial pressure cannot be excluded because of the risk of cerebral herniation, as might be the case here because of neurological symptoms and suspicion of a cerebral hemorrhage. Also, there is a risk of bleeding complications due to a platelet count below 50 000/mm³. If the CT -scan is normal and there is still an indication, a lumbar puncture can only be performed after prophylactic platelet infusion.

=====================================

Case (continued)

The clinical signs of bleeding and anaemia in the setting of thrombocytopenia made you wonder if platelets infusion is warranted.

When is a therapeutic platelet infusion indicated?

Feedback

Therapeutic platelet infusion does not only depend on the platelet count. In the acute setting, platelet infusion is indicated based both on bleeding severity and the etiology. Platelet infusion is generally recommended when bleeding is ≥ WHO grade 2 (see table).

Platelet infusion may not prevent or control bleeding if other contributing factors such as medications, an underlying disease state (e.g., uremia) that may interfere with platelet function or anticoagulants are not addressed simultaneously. Notably, several diseases such as disseminated intravascular coagulation or thrombotic thrombocytopenic microangiopathy preclude platelet transfusion as it may promote complications (1).

==================================

Case (continued)

The Ct-scan showed no signs of intracranial bleeding and was also without other abnormalities.

What are the most appropriate tests to make a diagnosis (multiple answers possible)

table

Feedback

Normocytic anemia with elevated reticulocytes, elevated (direct) bilirubin, and LDH are compatible with hemolytic anemia. The first step is to differentiate between immune- and non-immune-mediated hemolysis by a direct antiglobulin test (DAT).

Haptoglobin level will be low in case of any form of hemolysis but will not help to differentiate between causes.

Blood cultures should be done in case an infection is suspected (e.g., meningococcaemia may be accompanied by hemolytic anemia and thrombocytopenia).

A blood smear is helpful to detect non-immune structural red blood cell abnormalities that may suggest a diagnosis (e.g., spherocytosis or schistocytes) and explain at the same time the co-existing thrombocytopenia. A blood smear is also necessary to detect red blood cell infection (malaria, babesiosis); real-time PCR is sometimes available to make these latter diagnoses.

Searching for antiplatelet antibodies is not useful in ITP nor TTP diagnosis or management. To make a diagnosis of Evans syndrome a DAT suffices.

There are no features on urinalysis that will definitively point toward thrombotic microangiopathic anemia (TMA) as the cause of acute kidney failure (AKI). The classic presentation of “muddy brown” casts suggests acute tubular necrosis (ATN) and is evidence against TMA. However, other causes of AKI may be identified based on specific findings such as red blood cell casts, which are typical of glomerulonephritis.

======================================

Case (continued)

The direct antiglobulin test was negative, haptoglobin undetectable and the peripheral blood smear showed 40% schistocytes. A diagnosis of TMA was made. The urinary sediment showed a few leukocytes and a trace amount of protein.

What is the most likely form of TMA in this patient?

Feedback

Thrombotic thrombocytopenic purpura is the most likely cause of TMA in this patient, because of TMA in the presence of cerebral involvement.

There are no clues from the history that may suggest Shiga-toxin hemolytic uremic syndrome and there is no renal involvement.

DIC is absent because of the normal coagulation tests (PT and APTT) and fibrinogen levels.

Antiphospholipid syndrome (APS) is less likely because of the normal APTT (absence of lupus anticoagulant) and no history of autoimmune disease e.g., systemic lupus. Notably, APS can present with TMA syndrome during the catastrophic antiphospholipid syndrome. Antiphospholipid antibodies should always be assessed in the setting of TMA.

======================================

Case (continued)

A presumptive diagnosis of TTP was made. Signs suggestive of other TMA-associated conditions were lacking.

What therapy do you want to start, while awaiting the ADAMTS13 test results? (multiple answers possible)