Hema and Cancer PDF

# Hematologic Conditions ## Anemia - Red blood cells contain several hundred hemoglobin molecules which transport oxygen. - Oxygen binds to heme on the hemoglobin molecule. ### Symptoms of Anemia - **Eyes:** Yellowing - **Skin:** Paleness, coldness, yellowing - **Respiratory:** Shortness of brea...

# Hematologic Conditions ## Anemia - Red blood cells contain several hundred hemoglobin molecules which transport oxygen. - Oxygen binds to heme on the hemoglobin molecule. ### Symptoms of Anemia - **Eyes:** Yellowing - **Skin:** Paleness, coldness, yellowing - **Respiratory:** Shortness of breath - **Muscular:** Weakness - **Intestinal:** Changed stool color - **Central:** Fatigue, dizziness, fainting - **Blood vessels:** Low blood pressure - **Heart:** Palpitations, rapid heart rate, chest pain, angina, heart attack - **Spleen:** Enlargement ## Anemia Chart The following chart describes a decision tree for diagnosing anemia: | Cell Volume (MCV) | Type | Notes | |---|---|---| | < 80 | Microcytic Anemia | Continue to Serum Iron Studies | | 80 - 100 | Normocytic Anemia | Continue to Reticulocyte Count | | > 100 | Macrocytic Anemia | Megalocytes and segmented neutrophils on peripheral smear | ### Serum Iron Studies | Iron and Ferritin Levels | Type | Notes | |---|---|---| | Low iron and ferritin with high Total Iron Binding Capacity (TIBC) | Iron Deficiency Anemia | | | Low iron and ferritin with low TIBC | Anemia of chronic disease | | ### Reticulocyte Count | Count | Type | Notes | |---|---|---| | < 2% | Hypoproliferative | Leukaemias, Aplastic anemia, Pure red cell aplasia | | > 2% | Hyperproliferative | Haemorrhage, Haemolytic anaemias | ### Megaloblastic | Megaloblastic | Type | Notes | |---|---|---| | Present | Vitamin B12 and/or Folate deficiency, Drug-induced | | | Absent | Alcohol abuse, Myelodysplastic syndrome, Liver disease, Congenital bone marrow failure syndromes | | ## Polycythemia - A condition where the red blood cell count is high. - The person has a high concentration of red blood cells in the blood. ### Symptoms - Blurry vision - Pain in the chest - Itching - Headaches - Dizziness - Muscle pain - Hypertension - Ruddy complexion - Ringing in the ears (tinnitus) ## Algorithm for the Diagnosis of Polycythemia Vera 1. **Elevated hemoglobin or hematocrit** 2. **Elevated red cell mass** 3. **Red cell mass and plasma volume measurements** - Both normal → Proceed to normal red cell mass - Decreased plasma volume → Proceed to hypoxic erythrocytosis 4. **Normal red cell mass** - **O2 saturation > 93%** - **JAK2V617F positive** → Polycythemia vera - **JAK2V617F negative** → Proceed to serum erythropoietin level - **O2 saturation < 93%** → Hypoxic erythrocytosis ### Serum Erythropoietin Level - **Normal or low** → Polycythemia vera, EPO-receptor mutation, renal disease, tumors, high-affinity hemoglobins - **Elevated** → Renal disease, tumors, VHL mutation, high-affinity hemoglobins ### Hypoxic Erythrocytosis - **Causes:** Tobacco use, androgens, diuretics, pheochromocytoma ## Leukopenia - Low white blood cell count. ### Types of White Blood Cells - Basophils - Eosinophils - Lymphocytes - Monocytes - Neutrophils ### Symptoms of Leukopenia - Fever higher than 100.5 - Chills - Sweating ### Causes of Leukopenia - Blood cell or bone marrow conditions, like aplastic anemia and myelofibrosis. - Cancer and cancer treatments - Congenital problems, like Kostmann syndrome and myelokathexis - Infectious diseases, like HIV and tuberculosis - Autoimmune diseases, like lupus and rheumatoid arthritis - Vitamin and mineral deficiencies ## Leukocytosis - High white blood cell count. ### Table 4. Selected Conditions Associated with Elevations in Certain White Blood Cell Types | White Blood Cell Type | Conditions | |---|---| | Basophils | Allergic conditions, leukemias | | Eosinophils | Allergic conditions, dermatologic conditions, eosinophilic esophagitis, idiopathic hypereosinophilic syndrome, malignancies, medication reactions, parasitic infections | | Lymphocytes | Acute or chronic leukemia, hypersensitivity reaction, infections (viral, pertussis) | | Monocytes | Autoimmune disease, infections (Epstein-Barr virus, fungal, protozoan, rickettsial, tuberculosis), splenectomy | | Neutrophils | Bone marrow stimulation, chronic inflammation, congenital, infection, medication induced, reactive, splenectomy | ## Thrombocytopenia - Low platelet count. - Leads to easy bruising and bleeding. ### Platelet Count versus Risk of Hemorrhage | Platelet Count | Risk of Hemorrhage | |---|---| | > 100,000/μL | None | | 50,000-100,000/μL | No risk of spontaneous bleeding; may have bleeding with major trauma or surgery | | 20,000-50,000/μL | May have minor spontaneous bleeding; major bleeding uncommon except with major trauma or surgery | | 10,000-20,000/μL | Minor bleeding likely; some risk of major bleeding | | <5,000-10,000/μL | Significant risk of severe life-threatening bleeding | ### Recommended Physical Exercises and Corresponding Cutoff Platelet Values (Table 2) | Platelet Count | Recommend Exercise | |---|---| | < 10,000/μL | Limit activity. Patient may require a platelet transfusion, before resuming exercise. | | 10,000-20,000/μL | Exercise gently, without resistance. Sitting or standing exercises, gentle stretching, and walking may be allowed. | | 20,000-50,000/μL | Resistance equipment such as weights, elastic tubing, or theraband may be used. The patients may be allowed to walk more briskly and practice step-ups or stairs. | | 50,000-80,000/μL | Activities such as stationary cycling and golfing are acceptable. | | > 80,000/μL | The patient can perform vigorous resistance exercises and aerobic exercises such as biking or jogging. However, an appropriate protective gear should be used, and precautions must be taken to avoid accidental injury. | ### Causes of Thrombocytopenia | Category | Causes | |---|---| | Decreased production | Intoxication (alcohol), Viral infections (HIV, HCV, EBV, CMV), Bone marrow infiltration (leukemia, tumors etc), Radiation/chemotherapy, Drug induced, Nutrient deficiencies (B12, folate, copper), Hereditary | | Increased destruction/consumption | Immune thrombocytopenia, Thrombotic microangiopathy, Post transfusion purpura, Drug induced (heparin, quinine etc), DIC/trauma, Cardiopulmonary bypass | | Sequestration | Portal hypertension, Infiltrative diseases of the spleen | ## Thrombocytosis - High platelet count. - Can lead to blood clots . ### Causes of Thrombocytosis (SIGO FACE) - **S**plenectomy - **I**nfectious diseases - **G**lucocorticosteroids - **O**ncological diseases - **F**racture of large bones (femur, humerus, pelvic bones) - **A**cute Or Chronic Bleeding - **C**hronic inflammation (colitis, vasculitis, arthritis) - **E**xtensive surgery ### Complications of Essential Thrombocytosis - **Microvascular ischemia** - Migraine - Erythromelalgia - Transient ischemic attacks - **Macrovascular thrombosis** - Stroke - Acute coronary syndrome - Peripheral arterial occlusion - Digital gangrene - Deep venous thrombosis - Hemorrhage due to acquired von Willebrand disease - Transformation to acute leukemia ## Hemophilia A - A rare, X-linked recessive bleeding disorder. - Deficiency in Factor VIII. ### Causes of Hemophilia A - **Inherited:** Spontaneous mutation - **Acquired:** Development of antibodies to Factor VIII ## Hemophilia A- Family Inheritance Chart **Left side:** Father without hemophilia and carrier mother. **Right side:** Father with hemophilia and mother who is not a carrier. | Person | Father without hemophilia and carrier mother | Father with hemophilia and mother who is not a carrier | |---|---|---| | Father | XY | XY | | Mother | XX | XX | | Son | XY | XY | | Daughter | XX | XX | ## Hemophilia - Lack of clotting factor. - Reduces the body's ability to control bleeding. ### Explanation of Hemophilia - **Injury occurs:** Injury to the blood vessel results in bleeding. - Normal blood vessel constriction. - Clotting factors are activated. - **Normal:** Natural clotting factor helps form a strong platelet plug. - **Hemophilia:** Lack of natural clotting factor means only a weak platelet plug can form. - Incomplete fibrin mesh allows bleeding to continue. ### Severity of Hemophilia | Severity | % of Working Factor IX | |---|---| | Mild | 6-49% | | Moderate | 1-5% | | Severe | less than 1% | ## Treatment of Hemophilia ### Treatment of Hemophilia - Things to Know - **Walking out of pt room should know...** 1. Type of Hemophilia 2. Patient Weight 3. Factor Activity 4. Severity of Bleed 5. Type of Factor 6. Goal Replacement - **Factor Activity** - If patient does not know % intrinsic activity **ASSUME 0%**. - **Units of Factor VIII Required** - Weight (kg) x 0.5 x (% Activity Desired - % Intrinsic Activity) - **Units of Factor IX Required** - Weight (kg) x 1.0 x (% Activity Desired - % Intrinsic Activity) ### Treatment of Hemophilia - Factor Replacement | Level | Location | Factor Replacement | |---|---|---| | Mild - Moderate | Soft Tissue, Muscle, Hemarthrosis, Epistaxis | Up to 50% | | Severe | CNS, GI, Neck/Throat | Up to 100% | ### Treatment Goals - Maintain hemostasis - Prevent bleeding episodes - Prevent neuromuscular dysfunction - Prevent disability - Maximize function ## Hemophilia - Issues in Rehabilitation - Hemarthrosis and hematomas are common and occur spontaneously. This may lead to contractures. - Hinge joints are not surrounded by protective muscles making them more susceptible to injuries. - Mobilizer muscles may bleed easily because they are at work to produce a movement while stabilizer muscles serve only to hold body against gravity. ## Hemophilia - Physical Consequences - Patients with hemophilia with active bleeding or frequent bleeding may have the following: - Flexion deformities of the ankle, knees and hips - Lumbar lordosis - Plantarflexion of the ankle - Pelvic asymmetry due to leg-length discrepancy - Varying amount of muscle wasting ## Hemophilia - Exercise Considerations - Factor availability - Slow and steady progression - Begin with isometrics - Pain-free sessions - Every session is unique - Consider functional training - Proprioception training ## Cancer - A pathologic process characterized by dysregulated cell growth and systemic spread. ### Neoplastic Potential & Cancer - All tissue types have neoplastic potential and can be cancerous. - Tissues distinguished by rapid cell turnover, hormone sensitivity, and regular exposure to mutagens have a higher rate of malignant transformation. ### Disease Consideration - Staging - Metastasis - Prognosis ## Cancer Stages | Stage | Description | |---|---| | Stage 0 | Carcinoma in situ - Early form | | Stage I | Localized | | Stage II | Early locally advanced | | Stage III | Late locally advanced | | Stage IV | Metastasized | ## TNM - Pathologic Stage - **Primary Tumor (T)** - **TX:** Primary tumor cannot be evaluated. - **TO:** No evidence of primary tumor. - **Tis:** Carcinoma in situ (has not spread). - **T1, T2, T3, T4:** Size and/or extent of the primary tumor. - **Regional Lymph Nodes (N)** - **NX:** Regional lymph nodes cannot be evaluated. - **NO:** No regional lymph node involvement. - **N1, N2, N3:** Involvement of regional lymph nodes (number and/or extent of spread). - **Distant Metastasis (M)** - **MX:** Distant metastasis cannot be evaluated. - **MO:** No distant metastasis. - **M1:** Distant metastasis (cancer has spread to distant parts of the body). ## Benign vs. Malignant Tumors | Tumor Type | Characteristics | |---|---| | Benign | Slow growth rate, No infiltration, No metastasis, High patient survival rates after successful surgical removal | | Low-grade malignant, Locally aggressive, Borderline | Variable growth rate, Locally infiltrative, Low or no metastatic potential, Intermediate patient survival rates; tendency for local recurrence after successful surgical removal | | Malignant | Rapid growth rate, Infiltrative, Metastasizing, Poor patient survival rates; tendency for local and distant recurrence (metastasis) | ## The Hallmarks of Cancer - Evading apoptosis - Self-sufficiency in growth signals - Insensitivity to anti-growth signals - Sustained angiogenesis - Limitless replicative potential - Tissue invasion and metastasis ## Phases of Cancer ### Initial Diagnosis and Treatment - Aggressive treatment to eradicate disease - Goal of rehab is to limit functional impact of cancer treatment - Surveillance - Continuous monitoring for emerging treatment toxicities and cancer recurrence ### Recurrence - Screen for cancer treatment toxicities. - Proactively manage early-stage impairments ### Temporization - Control symptoms. - Prevent and proactively address disablement. ### Palliation - Preserve community integration. - Support and educate caregivers. - Maintain functional autonomy as feasible. ## Rehabilitation Planning - Anticipation of problem - Likely metastasis - Respond to treatment - Cumulative toxicities from treatment - Life expectancy - Symptom-oriented vs disease-modifying treatment strategy ## Rehabilitation Priorities During Cancer Phases (Box 20-1) ### Initial Diagnosis - Detect and manage acute morbidity from cancer treatments. - Address worsening of premorbid physical impairments. ### Surveillance - Physically recondition. - Detect and address delayed cancer treatment toxicities. - Promote reentry into vocational, social, and family roles. ### Recurrence - Screen for cancer treatment toxicities, given the increased risk. - Proactively manage early-stage impairments. ### Temporization - Control symptoms. - Prevent and proactively address disablement. ### Palliation - Preserve community integration - Support and educate caregivers - Maintain functional autonomy as feasible ## Pain and Fatigue - Pain and fatigue present the most consistent and challenging obstacles to successful rehabilitation. ## Pain - Prevalence is 28% among patients with newly diagnosed cancer, 50-70% among patients receiving anti-neoplastic therapy. - Usually due to tumor effects. - Could be acute or chronic. - Acute pain usually due to complications from surgery or radiotherapy. - Chronic pain could be due to tumor compressing visceral structures but most often due to bone metastasis. ## Considerations in Cancer Pain Management (Box 29-3) - Therapeutic reliance on high-dose opioid analgesia - Importance of disease-modifying analgesic approaches - Potential loss of enteral administration - Dynamic and rapidly progressive pain complaints - Multiple concurrent pain syndromes - Affective and organic psychopathology - Feasibility of permanent ablative procedures - Concurrent nociceptive and neuropathic pain ## Fatigue - Most common symptom experienced by cancer patients. ### Cancer-Related Fatigue - An unusual, persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning. ### Criteria for Cancer-Related Fatigue - Diminished energy - Increasing need for rest - Limb heaviness - Diminished ability to concentrate - Decreased interest in engaging in normal activities - Sleep disorder - Inertia - Emotional lability - Perceived problems with short term memory - Post-exertional malaise exceeding several hours ## Reversible Sources of Cancer Fatigue (Box 20-2) - Anemia - Insomnia or lack of restorative sleep - Cytokine release (e.g., tumor necrosis factor) - Hypothyroidism - Hypogonadism - Depression - Deconditioning - Steroid myopathy - Centrally acting medications - Altered oxidative capacity - Pain - Adrenal insufficiency - Cachexia ## Impairment in Cancer - Tumor Effects ### Paraneoplastic Syndrome - Rare disorders triggered by an altered immune system response to cancer. #### Pathophysiology - Antibodies against tumor mistakenly attack normal tissues. - Tumor produce hormones, hormone precursors, or enzymes that affect and/or destroy normal tissues. - Triggered during early stages of cancer. - Emergence of PNS in patient with known CA should warrant a work-up for recurrence or metastasis. - Fever of unknown origin is the most common presentation. ### Brain Tumor - Most commonly metastasis from lung cancer. - The most common symptoms in descending order are: Headache > Mental Disturbance > Focal Weakness > Gait Ataxia > Seizure. - Corticosteroid is the first line of treatment - Dexamethasone is the drug of choice. - Untreated patients have a median survival rate of 1 to 2 months. ### Bone Metastasis - Most common site of metastatic spread. - Bisphosphonates for boneサポート support. - High risk for pathologic fracture. - Surgical treatment. - Life expectancy > 1 month for weight-bearing bones. - Life expectancy > 3 months for non-weight-bearing bones. ### Epidural Spinal Cord Compression - Most common primary from breast, lungs, myeloma, and prostate. - Compresses the spinal cord or cauda equina. - Pain is the most common initial presentation exacerbated by Valsalva. - Thoracic spine is the most common site. ### Brachial Plexopathy - Most common source is from lungs and breast cancer. - Inferior trunk and medial cord commonly involved. - C8-T1 - Median and Ulnar nerves - Most disturbing symptom is pain (vs numbness in radiation plexopathy). ## Impairment in Cancer - Cancer Treatment ### Surgery - Affects normal tissue - Removal of unaffected nearby tissues for prevention of recurrence - Aesthetic issue - Mastectomy in breast CA - Complications (expected or unexpected), like injury to the recurrent laryngeal nerve in thyroid cancer. ### Radiation Therapy - Timing - Acute < 4 weeks post RT - Early 1-6 months post RT - Late > 6 months post RT - Adverse effects are mainly due to affected normal tissues. - Complications from radiation therapy depend on the site treated. ### Radiation Induced Myelopathy | Type | Characteristics | |---|---| | Early-onset myelopathy | Peak at 4-6 months. Resolves within 9 months. Clinical onset is marked by paresthesia that radiate from the cervical spine to extremities. Paresthesia typically symmetrical and does not follow a dermatomal distribution. | | Late-onset myelopathy | 9-18 months after completion of treatment. Irreversible onset of symptoms, typically begins with LE paresthesia followed by sphincter dysfunction and weakness. | ### Radiation-Associated Brain Injury - Timeline: Days, Weeks, Months, Years - **Days:** Edema, characterized by drowsiness, headache, nausea, vomiting, worsening of pre-existing focal neurologic symptoms - **Weeks:** Demyelination, characterized by headache, somnolence, fatigability, attention deficits, and short-term memory loss - **Months:** Necrosis, diffuse white matter injury, leukoencephalopathy, characterized by cognitive dysfunction, ataxia, confusion, dysarthria, seizures, dementia, and death ### Chemotherapy - Mainstay of anti-cancer therapy. #### General Uses - Induction therapy for advanced disease - Adjunct to treatment of localized tumor - Primary treatment of localized cancer - Direct installation into site of specific body region affected #### Types - **Induction:** For advanced disease for which no other treatment exists - **Adjuvant:** Done after local control is achieved through surgery or radiation when no obvious tumor is present. The goal is to eliminate undetectable micro-metastases or risk of recurrence. - **Neoadjuvant:** Can be used before surgery to reduce tumor size to decrease the degree of anatomic disruption. #### Side Effects - **Bleomycin:** Pulmonary fibrosis - **Cisplatin:** Ototoxicity, nephrotoxicity - **Adriamycin/Daunarubicin/Doxarubicin:** Cardiotoxicity - **Vincristine/Vinblastine:** Peripheral neuropathy - **Cyclophosphamide:** Hemorrhagic cystitis ### Lymphedema - Damaged lymphatics either from surgical removal or from radiotherapy - Treatment is complex decongestive therapy (CDT) #### Stages of Lymphedema - **Reductive phase:** Decrease lymphedema volume. - **Maintenance phase:` Teach self-management techniques #### Reductive Phase - 45 minutes of manual lymphatic drainage (MLD) to sequester and transport lymph. - Highly specialized technique designed to enhance the sequestration and transport of lymph - Application of compression bandages for 21-24h/day - Remedial exercises. - Repetitive movements designed to encourage rhythmic, serial muscle contractions in lymphedematous territories. #### Maintenance Phase - Compression garments are used during the day. - Compression bandages overnight. - Remedial exercises daily while bandaged. - MLDs as needed.