UMEM Educational Pearls - Hematology/Oncology

Evidence is mounting that individuals with active or past history of cancer are at increased risk for acute cardiovascular events such as as acute myocardial infarction.  This secondary analysis from the APACE (Advantageous Predictors of Acute Coronary Syndromes Evaluation) study- a multicenter, international, prospective diagnostic study looked at the prevalence of MI in patients with history of cancer presenting to the ED with acute chest pain, diagnostic accuracy of high-sensitivity troponins and diagnostic algorithms (European Society of Cardiology algorithm- see paper for details), among a few other parameters.  

Take home points:

• There was substantially higher prevalence of AMI in patients with cancer. 
• The diagnostic performance of the high-sensitivity troponin algorithms was reduced.

Translation to practice:

Be more conservative with cancer patients presenting to the ED with acute chest pain!

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The routine use of ultrasound guidance has decreased CVC-related complications, especially in patients at risk for bleeding. To this day, however, platelet transfusion threshold guidelines range widely from 20,000 - 50,000 platelets per cubic millimeter, and also lack good-quality evidence.

This multicenter, randomized, controlled, noninferiority trial randomly assigned patients with severe thrombocytopenia (platelet count 10,000 to 50,000 per cubic millimeter) to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. 

Author's Conclusions: Withholding prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did NOT meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion.

BUT…taking a closer look at this study reveals many nuanced points. Many of the study patients were heme/onc patients possibly having bleeding issues outside of low platelets, bleeding complications trended with subclavian and femoral locations as well as lower initial platelet counts. All this suggests that additional studies need to be done to move towards more specific evidenced-based guidelines.

To read more details on the study, click the referenced link.

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Hot off the NEJM press, published November 11, 2023:

Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia (Carson, Brooks, Hebert, et al Myocardial Ischemia and Transfusion (MINT) Investigators)

• Phase 3 interventional trial
• Adult patients with STEMI or NSTEMI and Hgb <10 g/dL were randomly assigned to either of two strategies
  • restrictive transfusion- threshold of 7-8 g/dL (transfusion was permitted but not required when the hemoglobin level was less than 8 and was strongly recommended when the level was less than 7 or when anginal symptoms were not controlled with medications)
  • liberal transfusion- threshold of 10 g/dL
• Primary outcome measured was recurrent MI or death at 30 days

3504 pateints were included in this study. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group. More specifically, death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy; myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively.

Conclusions from the study: Liberal transfusion strategy did NOT significantly reduce the risk of recurrent MI or death at 30 days. 

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Question

Treatment of neutropenic fever is evolving, especially in the context of multidrug-resistant (MDR) organisms. This article reviews an update on best practices and describes two approaches to antimicrobial therapy- "escalation" and "de-escalation". Escalation begins with a narrow spectrum of antimicrobials and increases based on patient response, suitable for uncomplicated cases. De-escalation starts with broad-spectrum antibiotics and narrows down, recommended for complicated cases. The choice depends on the institution's MDR prevalence. Initial antimicrobials like cefepime or carbapenems are selected based on resistance rates. De-escalation timing varies per guidelines, but clinical trials support its safety and efficacy. Benefits include reducing C. difficile risk, antimicrobial resistance, and complications. Despite these advantages, some centers lack explicit de-escalation guidance, emphasizing the need for clear protocols to optimize patient outcomes by minimizing antibiotic therapy duration.

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Management of Heparin-Induced Thrombocytopenia (HIT)

HIT occurs when antibodies form to a Heparin-Platelet Factor 4 (PF4) complex in patients who have been exposed to Heparin. 

The main clinical manifestation is thrombosis (arterial/venous). Treatment is unique in that only certain medications can be used.

Medical Management options in HIT:

• Direct thrombin inhibitors (DTI). The main ones used in clinical practice include Argatroban and Hirudin. These drugs work by directly binding to thrombin (fibrin bound) and inhibiting it. The drugs are reliable and safe. Hirudin may initiate an allergic reaction in patients who have been exposed and is renally cleared (so shouldn't be used in ESRD or lower GFRs)
• Fondaparinux (Arixtra). Can be given subcutaneously. More expensive. Also approved for once daily treatment of DVT/PE

So, when a patient with a history of HIT shows up in the ED with a DVT/PE or other thrombotic problem, these are your mainstay drugs.

Multiple Myeloma + Altered Mental Status=Hyperviscosity Syndrome

Although the differential diagnosis of altered mental status is quite extensive, a patient with multiple myeloma and altered mental status should prompt consideration of one important, albeit not too common, condition.....hyperviscosity syndrome.

Some important pearls:

• This syndrome occurs when excessive amounts of protein (immunoglobulin) are secreted by myeloma (plasma) cells.
• Excessive circulating protein leads to sludging and ischemia in lung and brain tissue, lesding to hypoxia and altered mental status, respectively.
• You will only pick up this diagnosis by thinking about it, so multiple myeloma + altered mental status = hyperviscosity syndrome
• Treatment is with IVF and plasmapheresis (heme onc consult)
• And don't forget common stuff, like stroke, subdural hematomas, meningitis, etc.

A neutropenic cancer patient that presents with right lower quadrant abdominal pain, fever, and bloody diarrhea should raise suspicion for typhlitis (necrotizing colitis, cecal inflammation). This most commonly occurs in patients with hematologic malignancies who have been treated with cytotoxic agents. This condition is high risk and is associated with high morbidity and mortaiity.

Treatment:

• Broad-spectrum antibiotics
• CT scan of the abdomen and pelvis
• Surgical consultation
• Usually requires ICU admission

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Just a quick remainder that Thrombotic thrombocytopenia Purpura, TTP, is typically described as a pentad of symptoms:

1. Neurological symptoms such as altered mental status, stroke, or headache
2. Renal failure
3. Fever
4. Thrombocytopenia (low platelets) associated with purpura
5. Microangiopathic hemolytic anemia

Not all symptoms need to be present and it would be rare for you to see the full pentad.  Consider the diagnosis and request that the lab due a manual differentiation or blood smear.  It is there that they will notice schistocytes, fragmented RBCs, that will help clinch the diagnosis.

Most cases of TTP are idiopathic (~60%) but secondary TTP is known to occur with cancer, pregnancy, HIV, bone marrow transplantation, immunospressive drugs like cyclosporin and tacrolimus, and platelet aggregation inhibitors such as cloperidol.

Treatment consists of plasmapheresis, plasma exchange, immunospression with steroids, Rituximab, and other chemotherapies.