Plasma

Multiple Myeloma (MM)

Definition

  • Multiple myeloma is a monoclonal plasma cell neoplasm in the bone marrow.

  • It is the most common primary malignancy of bone; metastatic cancer is the most frequent malignant lesion overall.

  • Plasma cells produce unregulated immunoglobulins (usually IgG or IgA) that are ineffective against infections but can cause kidney damage.

Presentation

  • Bone pain due to pathologic fractures from osteoclast activating factor (OAF) results in lytic lesions.

  • Common causes of death include renal failure and infections due to ineffective immunoglobulin production.

  • Symptoms include:

    • Hyperuricemia from plasma cell turnover.

    • Anemia from marrow infiltration with plasma cells.

    • Renal failure from accumulating immunoglobulins and Bence-Jones protein, further impacted by hypercalcemia.

Diagnostic Tests

  • X-ray shows lytic lesions (especially in vertebrae and skull).

  • Serum protein electrophoresis (SPEP) may show an IgG (60%) or IgA (25%) M-spike, indicating monoclonality.

  • Bone marrow biopsy confirms myeloma if clonal plasma cells exceed 10%.

  • Additional tests show hypercalcemia, elevated BUN and creatinine, and urine immunoelectrophoresis indicating Bence-Jones protein presence.

Treatment

  • Initial therapy often involves dexamethasone combined with lenalidomide or bortezomib.

  • Melphalan for older patients unable to tolerate side effects.

  • Autologous bone marrow transplant is typically the best option for patients under 70 after induction chemotherapy.

  • Daratumumab, an anti-CD38 drug, is used for relapse cases.

Monoclonal Gammopathy of Unknown Significance (MGUS)

  • Characterized by overproduction of a particular immunoglobulin without myeloma symptoms (e.g., bone lesions, renal failure).

  • Common in older patients with IgG or IgA spikes found on SPEP.

  • Need a bone marrow biopsy to rule out progression to myeloma.

Waldenström Macroglobulinemia (WM)

  • A plasma cell malignancy producing excessive monoclonal IgM antibodies.

  • Causes include:

    • Hyperviscosity syndrome leading to blurry vision and vertigo.

    • Neoplastic infiltration resulting in hepatosplenomegaly, lymphadenopathy, and cytopenias.

  • Diagnosed through bone marrow biopsy showing >10% clonal B cells and an M-spike of IgM detected via SPEP.

Bleeding Disorders

Mechanisms

  • Formation of insoluble fibrin mesh; affected by various drugs (e.g., aspirin, clopidogrel) that inhibit platelet aggregation.

  • Inhibition of TXA2 synthesis causes impaired hemostasis.

Types of Bleeding

  • Platelet bleeding: Superficial (e.g., epistaxis, bruising).

  • Factor bleeding: Deep bleeding (e.g., hemarthrosis).

Hemophilia

  • Includes Hemophilia A (factor VIII deficiency) and B (factor IX deficiency), characterized by delayed bleeding, particularly in males.

Diagnostic Tests for Hemophilia

  • PT normal, aPTT prolonged.

  • Mixing studies correct the aPTT to normal.

Treatment of Hemophilia

  • Mild Hemophilia A: Desmopressin is used to release factor VIII.

  • Severe deficiency treatment: Replacement therapy of the specific factor deficiency is required.

Vitamin K Deficiency

  • Leads to decreased synthesis of factors II, VII, IX, and X.

  • Commonly due to inadequate intake, malabsorption, or liver disease.

Clinical Presentation

  • Bleeding may mimic hemophilia; common at venipuncture sites.

Diagnosis

  • Elevated PT and PTT, corrected with vitamin K administration.

Von Willebrand Disease (VWD)

  • Most common inherited bleeding disorder with decreased levels of von Willebrand factor affecting platelet function.

Diagnostic Tests

  • Normal platelet count with increased bleeding time, particularly after aspirin use.

Treatment

  • Desmopressin acetate (DDAVP) can be administered to manage mild cases.

Disseminated Intravascular Coagulation (DIC)

  • Results from pathologic activation of the coagulation cascade leading to microthrombi, ischemia, and bleeding.

Clinical Presentation

  • Widespread bleeding from various sites, possible hemolysis.

Diagnosis

  • Elevated PT, aPTT, low platelet count, and increased d-dimer levels.

Treatment

  • Replace platelets and clotting factors using FFP if bleeding is significant.

Hypercoagulable States/Thrombophilia

Factor V Leiden

  • The most common inherited cause of hypercoagulability, often noted with a family history.

Heparin-Induced Thrombocytopenia (HIT)

  • Can occur with both unfractionated and low molecular weight heparin.

  • Characterized by a >50% reduction in platelet count after 5-10 days of heparin use.

Treatment

  • Immediate cessation of heparin products and switching to direct thrombin inhibitors.

Transfusion Reactions

Major Blood Group (ABO) Incompatibility

  • Sudden onset of severe symptoms during the transfusion indicates acute hemolytic reactions.

Minor Blood Group Reaction

  • Presents with fever and jaundice occurring 7 to 14 days after transfusion.

Transfusion-Related Acute Lung Injury (TRALI)

  • Occurs due to donor antibodies causing lung complications.

Management of Reactions

  • Supportive care and hydration for serious reactions.