In our last post, we covered the diagnostic framework for multiple myeloma — the CRAB criteria and the 2014 SLiM biomarker update that transformed how and when we intervene. Today, we bring that framework to life with a real case that illustrates why keeping an open mind is just as important as knowing the criteria.
The Case
Patient: 78-year-old male Chief Complaint: 2 days of excessive nosebleeds and gum bleeding No prior bleeding history. No anticoagulant use. |
On initial evaluation, the most striking finding was a PT and PTT that exceeded the laboratory's measurement capability — off the charts. And yet, two key findings that would typically explain this were conspicuously absent:
Fibrinogen was normal — ruling out disseminated intravascular coagulation (DIC)
Platelet count was normal — ruling out thrombocytopenic causes
Fresh frozen plasma (FFP) was administered and the patient responded — but only transiently. Coagulation studies worsened once the effect wore off. This pattern — temporary correction with FFP — pointed toward a factor inhibitor or a circulating substance consuming or neutralizing coagulation factors.
Key Laboratory Findings
Lab Test | Patient's Value | Clinical Significance |
PT / PTT | Beyond measurable range | Severe coagulopathy — not explained by common causes |
Fibrinogen | Normal | Rules out DIC — key negative finding |
Platelet count | Normal | Rules out thrombocytopenia |
IgG level | >6 g/dL | Markedly elevated M protein |
Kappa free light chain | >1,000 mg/dL | Consistent with active plasma cell dyscrasia |
SPEP | IgG kappa M spike | Confirms monoclonal gammopathy |
Working It Up: The Diagnostic Pivot
With DIC and thrombocytopenia off the table, and coagulopathy that didn't sustain correction, the team broadened the differential. SPEP and serum free light chains were sent — and the results were striking:
🔬 IgG level: >6 g/dL 🔬 Kappa free light chain: >1,000 mg/dL 🔬 SPEP: IgG Kappa M spike |
These findings confirmed IgG kappa multiple myeloma. But this patient hadn't come in with bone pain, hypercalcemia, renal failure, or anemia. He came in bleeding.
So How Does Myeloma Cause Coagulopathy?
This is where it gets mechanistically interesting. In myeloma, the massively elevated M protein — in this case IgG — can interfere with coagulation through several pathways:
Paraprotein interference: The M protein can directly inhibit coagulation factor activity, particularly factors V, VIII, and thrombin.
Hyperviscosity: At very high M protein levels, increased plasma viscosity disrupts normal hemostasis and endothelial interaction.
Acquired factor inhibitors: Rare cases involve antibody activity of the M protein directed against specific coagulation factors — functionally acting as an inhibitor.
The transient response to FFP is explained by this mechanism: FFP replenishes coagulation factors, but as long as the inhibitory or interfering paraprotein remains, factors are rapidly neutralized again. Treating the myeloma is treating the coagulopathy.
🧠 The Takeaway CRAB + SLiM criteria tell us what myeloma classically looks like — but myeloma is not always a classic disease. This case is a reminder that: |
Unexplained coagulopathy — especially with normal fibrinogen and platelets — should prompt consideration of a plasma cell dyscrasia
SPEP and free light chains are low-barrier, high-yield tests that should be part of the unexplained bleeding workup
Transient response to FFP without a clear underlying cause is a diagnostic signal, not just a management frustration
Myeloma can present before CRAB criteria develop — and this patient's diagnosis would have been missed if the workup stopped at "coagulopathy NOS"
If this case resonated with you, revisit the Multiple Myeloma: The Basics post for the full diagnostic framework — it's a helpful companion to this case.
As always, reply to this email with any questions or topic requests. More cases and deep dives coming soon.
— Dr. Astha Thakkar
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