What are the clinical differences between polycythemia, Thrombotic Thrombocytopenic Purpura (TTP), Disseminated Intravascular Coagulation (DIC), and multiple myeloma?

Clinical Differences Between Polycythemia, TTP, DIC, and Multiple Myeloma

Polycythemia vera (PV), thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), and multiple myeloma (MM) are distinct hematological disorders with unique clinical presentations, laboratory findings, and management approaches.

Polycythemia Vera

Clinical Presentation

• Primary feature: Erythrocytosis (elevated red blood cell count)
• Associated symptoms:
  • Thrombocytosis
  • Leukocytosis
  • Splenomegaly
  • Pruritus (especially after warm baths)
  • Microcirculatory symptoms (headache, dizziness, visual disturbances)
  • Thrombotic events (both arterial and venous)

Laboratory Findings

• Elevated hematocrit (>45%)
• Elevated hemoglobin
• Increased red cell mass
• JAK2 mutation (expected in almost all cases)
• Normal or elevated platelet count
• Normal or elevated white blood cell count

Risk Stratification

• High risk: Age >60 years or history of thrombosis
• Low risk: Absence of both risk factors 1, 2

Thrombotic Thrombocytopenic Purpura (TTP)

Clinical Presentation

• Pentad (classic but not always present):
  • Microangiopathic hemolytic anemia
  • Thrombocytopenia
  • Neurological abnormalities
  • Renal dysfunction
  • Fever
• Purpura and petechiae
• Neurological symptoms (confusion, headache, seizures)

Laboratory Findings

• Severe thrombocytopenia
• Schistocytes on peripheral blood smear
• Elevated LDH
• Negative direct Coombs test
• ADAMTS13 deficiency (acquired or congenital)
• Normal coagulation studies (PT, PTT)

Special Considerations

• May be secondary to malignancy (especially adenocarcinoma)
• Patients with malignancy-associated TTP typically have:
  • Longer duration of symptoms
  • Respiratory symptoms
  • Higher LDH levels
  • Poor response to plasma exchange 3

Disseminated Intravascular Coagulation (DIC)

Clinical Presentation

• Always secondary to an underlying disorder (e.g., malignancy, sepsis)
• Can present as:
  • Bleeding (mucosal, surgical sites, venipuncture sites)
  • Thrombosis (microvascular and macrovascular)
  • Combination of both

Subtypes in Cancer-Associated DIC

1. Procoagulant DIC:

   • Predominant in pancreatic cancer and adenocarcinomas
   • Features of arterial ischemia (patchy skin discoloration, poor digital circulation)
   • Venous thrombosis or pulmonary embolism

2. Hyperfibrinolytic DIC:

   • Predominant in acute promyelocytic leukemia and metastatic prostate cancer
   • Widespread bruising
   • Bleeding from mucosal surfaces, CNS, lungs, GI tract

3. Subclinical DIC:

   • Laboratory abnormalities without obvious clinical symptoms 4

Laboratory Findings

• Thrombocytopenia
• Prolonged PT and PTT
• Decreased fibrinogen
• Elevated D-dimer and fibrin degradation products
• Schistocytes may be present

Multiple Myeloma

Clinical Presentation

• CRAB features:
  • Calcium elevation (hypercalcemia)
  • Renal insufficiency
  • Anemia
  • Bone lesions (lytic lesions, pathologic fractures)
• Fatigue
• Bone pain
• Recurrent infections
• Neurological symptoms (spinal cord compression)
• Hyperviscosity syndrome (rare)

Laboratory Findings

• Monoclonal protein (M-protein) in serum and/or urine
• Anemia (present in 73% of patients)
• Elevated serum creatinine
• Hypercalcemia
• Elevated beta-2 microglobulin
• Abnormal serum free light chain ratio
• Bone marrow with ≥10% clonal plasma cells 4, 5

Risk Stratification

• Revised International Staging System combines:
  • Serum β2 microglobulin
  • Albumin
  • LDH
  • High-risk cytogenetic abnormalities 5

Key Differential Features

Blood Cell Counts

• PV: Elevated RBCs, normal/elevated platelets and WBCs
• TTP: Normal RBCs (but hemolysis), severely decreased platelets
• DIC: Variable RBCs, decreased platelets
• MM: Decreased RBCs (anemia), normal/decreased platelets and WBCs

Coagulation Profile

• PV: Usually normal
• TTP: Normal PT/PTT
• DIC: Prolonged PT/PTT, decreased fibrinogen, elevated D-dimer
• MM: Usually normal (unless associated with amyloidosis)

Organ Involvement

• PV: Primarily vascular complications
• TTP: Primarily neurological and renal
• DIC: Multiple organ systems (depending on thrombosis/bleeding)
• MM: Primarily bone, kidney, bone marrow

Disease Course

• PV: Chronic with median survival of 14-15 years
• TTP: Acute, life-threatening without prompt treatment
• DIC: Acute, severity depends on underlying cause
• MM: Progressive with median survival of 5-7 years with current therapies

Clinical Pitfalls to Avoid

1. Misdiagnosing malignancy-associated TTP: Patients with disseminated malignancy presenting with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as primary TTP. Consider bone marrow biopsy in TTP patients with atypical features or who fail to respond to plasma exchange 3.

2. Overlooking subclinical DIC: Laboratory abnormalities may be present without obvious clinical symptoms in cancer patients 4.

3. Confusing secondary thrombocytosis with ET: Reactive thrombocytosis can mimic essential thrombocythemia but lacks the driver mutations (JAK2, CALR, MPL).

4. Missing MGUS progression to MM: Patients with monoclonal gammopathy of undetermined significance require monitoring as they can progress to multiple myeloma.

5. Attributing anemia in MM solely to bone marrow infiltration: Renal insufficiency and other factors also contribute to anemia in MM patients.