Clinical Manifestations in Hematology

Disseminated Intravascular Coagulation (DIC)

• DIC is a serious disorder involving bleeding and blood clots.
• It results from abnormally fast clotting and anticlotting processes in response to disease or injury.
• DIC is characterized by excessive bleeding due to depleted platelets and clotting factors.
• An underlying disease or condition always causes DIC.
• Treatment focuses on treating the underlying cause to resolve DIC.

Pathogenesis of DIC

• Widespread activation of coagulation
• Endothelial damage
• Generalized platelet aggregation
• Microthrombi form in the circulation, blocking blood flow.

Events Leading to Thrombosis and Bleeding in DIC

• Circulating thrombi obstruct microcirculation in organs.
• Fibrinolysis in microcirculation
• Consumption of platelets, AT III, fibrinogen, and clotting factors
• Consumption of coagulation proteins

Bleeding Manifestations

• Integumentary: Pallor, petechiae, purpura, oozing blood, hematomas
• Respiratory: Hemoptysis
• Cardiovascular: Hypotension
• Gastrointestinal: Upper and lower GI bleeding, abdominal distension
• Bloody stools, hematuria, changes in mental status, musculoskeletal complaints (bone and joint pain).

Thrombotic Manifestations

• Fibrin or platelet deposition in microvasculature
• Integumentary changes (e.g., cyanosis)
• Ischemic tissue necrosis (e.g., gangrene, hemorrhagic necrosis)
• Respiratory changes (e.g., tachypnea, dyspnea)
• Pulmonary emboli
• Acute respiratory distress syndrome (ARDS)
• Cardiovascular changes (ECG changes, venous distension)
• Gastrointestinal changes (abdominal pain, paralytic ileus)
• Urinary changes (oliguria leading to renal failure)

Acute vs Chronic DIC

• Acute DIC: Develops suddenly, severe consumptive coagulopathy leading to hemorrhage, and frequent organ failure.
• Chronic DIC: Reflects a compensated state, more frequently observed in solid tumors and large aortic aneurysms, and clinical manifestations vary from easy bruising to thrombosis.

Diagnostic Tests for DIC

• Prolonged PT, PTT, APTT
• Reduced platelets, fibrinogen
• Fibrin split products (FSPs)
• Factor assays (factors V, VIII, X, XIII)
• D-dimers (cross-linked fibrin fragments)
• Antithrombin III (AT III)
• Protein C and S (antithrombotic proteins)
• Plasminogen, tissue activator
• Peripheral blood smear

Management of DIC

• Stabilize the patient (e.g., oxygenation, volume replacement)
• Treat the underlying cause of DIC.
• Provide supportive care for the manifestations.
• No therapy for DIC is needed if it is chronic and the patient isn't bleeding.
• Treatment of the underlying disease can reverse the DIC (e.g., chemotherapy for malignancy).
• When the patient bleeds, direct therapy towards providing support with blood products and treat the primary cause.

Therapy for DIC

• Treat the cause.
• Use Heparin and AT III.
• Fresh-frozen plasma, cryoprecipitate, and red blood cell transfusions.
• Platelet transfusions
• Hemodialysis for acute renal failure

Leukemia

• Malignant disorders affecting the blood and blood-forming tissues.
• Commonly affects the bone marrow, lymph system and spleen.
• Often thought of as a childhood disease
• Adults are affected 10 times more than children
• Characterized by diffuse replacement of bone marrow with proliferating leukocyte precursors resulting in dysfunctional cells
• Progressive disease if untreated.

Clinical Manifestations of Leukemia

• Symptoms result from complications of leukemic cells infiltrating organs including bone marrow.
• Fatigue and weakness
• Headache, mouth sores, anemia, bleeding, fever, infection
• Hepatomegaly (enlarged liver)
• Lymphadenopathy (enlarged lymph nodes)
• Bone pain, meningeal irritation, oral lesions (chloromas)
• Marrow-suppression

Diagnostics for Leukemia

• Low RBC count, Hb, and Hct; low platelet count; low to high WBC count (myeloblasts); high LDH; greatly hypercellular bone marrow with myeloblasts
• Peripheral blood evaluation
• Bone marrow examination (morphological, histochemical, immunological, and cytogenetic methods)
• Lumbar puncture and CT scan to see presence of leukemic cells outside the blood and bone marrow
• Specific cytogenetic abnormalities

Care Management for Leukemia

• Addressing physical and psychosocial needs of the patient, and their family.
• Addressing comorbid conditions affecting treatment decisions
• Maximizing patient's physical functioning
• Teaching patients that adverse effects of treatment are usually temporary
• Encouraging patients to discuss quality-of-life issues
• Assessing laboratory data
• Being knowledgeable about all medications

Chemotherapy for Leukemia

• Combination chemotherapy used as the mainstream treatment.
• Has 3 purposes: overcoming drug resistance
• reducing drug toxicity by using multiple drugs for varying toxicities
• interrupting cell growth points during the cell cycle
• Specific chemotherapy regimens, CBC check-ups, and schedules vary according to each patient and their cycle.

Bone Marrow & Stem Cell Transplantation for Leukemia

• Aims to totally eliminate leukemic cells from the body.
• Uses combinations of chemotherapy, sometimes with whole body irradiation, to achieve elimination.
• Replaced with healthy cells from an HLA matched donor.
• Possible options include siblings, volunteers, identical twins, or patient's own stem cells removed beforehand via autologous or allogeneic procedures.

Chemotherapy for Leukemia - Categories and Examples

• Alkylating agents: Damage DNA (Cisplatin, Adriamycin)
• Antitumor Antibiotics: DNA synthesis inhibition (Methotrexate, Docetaxel)
• Antimetabolites: Impeding cell cycle (Vincristine)
• Taxanes: Interrupt cell cycle (Imatinib)
• Monoclonal Antibodies: Antibody targeting specific proteins (Rituximab, Trastuzumab)
• Tyrosine Kinase Inhibitors: Inhibit tyrosine enzymes (Imatinib)

Adverse Reactions to Leukemia Treatment

• Antineoplastic medication causes rapid destruction of normal cells, resulting in increased uric acid.
• Mucositis, alopecia, anorexia, nausea and vomiting, diarrhea, anemia, neutropenia, thrombocytopenia, and neuropathy.

Neutropenia

• Decreased neutrophils
• Increased risk of infection
• Can be gradual or sudden
• Resulting from other conditions or diseases
• Drug therapy, hematological disorders, autoimmune disorders, infections, or hemodialysis
• Clinical manifestations include missing signs of infection and sudden presentation of septic shock

Clinical Manifestations of Neutropenia

• Signs of inflammation (redness, heat, swelling) may not be present.
• Absence of pus formation.
• Low-grade fever can indicate infection and lead to septic shock.
• Fever > 38°C and neutrophil count < 0.5 x 10⁹/L is a medical emergency.

Hodgkin's Lymphoma

• Malignant lymphoma characterized by proliferation of abnormal giant, multinucleated Reed-Sternberg cells.
• Located in lymph nodes.

Clinical Manifestations of Hodgkin's Lymphoma

• Insidious onset, with lymph node enlargement (movable, nontender)
• B-symptoms (fever, night sweats, weight loss).
• Advanced stages include hepatomegaly, splenomegaly, or anemia depending on location.
• Depending on the site, symptoms may include superior vena cava syndrome or abdominal masses interfering with renal function if retroperitoneal and/or jaundice from liver involvement.
• Bone involvement might lead to bone pain
• Spinal cord compression potentially leading to paraplegia.

Staging of Hodgkin's Lymphoma

• Stage I: Involvement of one lymph node group on one side of the diaphragm.
• Stage II: Involvement of two or more lymph node groups on one side of diaphragm.
• Stage III: Involvement of lymph node groups on both sides of the diaphragm.
• Stage IV: Spread to organs or bone marrow.

Treatment of Hodgkin's Lymphoma

• Radiation therapy is effective in the majority of patients in stages I and II.
• Combination chemotherapy (e.g., MOPP and ABVD) is used for advanced stages.

Non-Hodgkin's Lymphoma (NHL)

• Varies from slowly developing to rapidly progressive lymphomas.
• Types include Burkitt's, diffuse large B-cell, and follicular lymphoma.
• Accounts for 90% of lymphomas are B-cells and 10% of lymphomas are T-cells.
• No single hallmark.
• NHL involves lymphocytes arrested at various stages of development.

Collaborative Care for NHL

• Treatment is usually chemotherapy +/- radiation.
• More aggressive lymphomas are more responsive to treatment.
• Chemotherapy regimens include CHOP, CVP, and COPP.
• Biological therapy options include alpha interferon, rituximab, and ibritumomab tiuxetan (Zevalin).

Complete Remission in NHL

• Complete remissions are uncommon
• Most respond with improvement and alleviation of adenopathy and symptoms.
• Radiation alone can be sufficient for localized stage I or II disease.
• For advanced disease, "watchful waiting" approach to assess disease progress.

Multiple Myeloma

• Malignant tumor of plasma cells within the bone marrow, arising from a single clone.
• Accounts for more than 40% of malignant tumors of the bone.

Clinical Manifestations of Multiple Myeloma

• Bone pain, especially ribs, spine, and pelvis
• Weakness and fatigue
• Recurrent infections
• Urinalysis shows Bence Jones proteinuria
• Osteoporosis
• Elevated calcium and uric acid levels
• Kidney failure
• Spinal cord compression

Disorders of the Spleen

• Spleen enlargement can cause sequestration of blood products.
• Removal of the spleen predisposes to infection potential.
• Rupture may cause radiating pain

Hemochromatosis

• Hereditary genetic condition where excessive iron is deposited in organs.
• No evident signs of disease until middle age.
• Men have more complications than women.
• Treatment is phlebotomy
• Can have acquired form, common in alcoholics

Hemophilia

• Two inherited disorders (A and B).
• Hemophilia A caused by lack of factor VIII.
• Hemophilia B (Christmas disease) caused by lack of factor IX.
• Men get this disease while women are carriers.
• The main issue is bleeding, especially into joints, resulting in swelling and pain.
• Can bleed with or without trauma.

von Willebrand Disease

• Common bleeding disorder that affects males and females equally.
• von Willebrand factor (vWF) is needed for the proper activity of factor VIII.
• Can lead to bleeding, especially nosebleeds, excessive bleeding from cuts, heavy menstruation, and postoperative bleeding issues.
• Prolonged bleeding times are common.
• Treatment includes treatment (similar to hemophilia) and DDAVP (increases factor VIII).
• Cryoprecipitate may be required prior to major surgeries.

Thrombocytopenia

• Reduction of platelets below 150 x 10⁹/L
• Immune thrombocytopenic purpura
• Heparin-induced thrombocytopenia.

Apheresis

• AKA Plasmapheresis; removes blood components through centrifuge
• Can obtain platelets, white blood cells, or harvest stem cells for transplant.

Test your knowledge on clinical manifestations associated with hematological disorders, including neutropenia, Hodgkin's disease, and Non-Hodgkin's lymphoma. This quiz will assess your understanding of diagnostic tests and supportive care strategies in these conditions.