Hematology and Cancer Conditions PDF

# HEMATOLOGIC CONDITIONS Mayla C. Wahab, RPH, MD, MMHA, FPARM ## Anemia - A diagram of a red blood cell. The red blood cell is composed of a red center and a thin red ring. - Red blood cells contain several hundred hemoglobin molecules, which transport oxygen. - A diagram of a hemoglobin molecu...

# HEMATOLOGIC CONDITIONS Mayla C. Wahab, RPH, MD, MMHA, FPARM ## Anemia - A diagram of a red blood cell. The red blood cell is composed of a red center and a thin red ring. - Red blood cells contain several hundred hemoglobin molecules, which transport oxygen. - A diagram of a hemoglobin molecule, which has several small, oval sections. The sections are connected by thin fibers. Oxygen binds to the heme on the hemoglobin molecule. ## Symptoms of Anemia - **Red = In severe 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 - **Examination of FBC and peripheral bloodsmear**: - **MCV < 80**: Microcytic anemia - **Serum iron studies** - Low iron and ferritin with high TIBC: Iron deficiency anemia - Low iron and ferritin with low TIBC: Anemia of chronic disease - **Mentzer index (MCV/RBC) < 13**: Thalassaemia - **MCV 80 - 100**: Normocytic anemia - **Reticulocyte count**: - < 2% (hypoproliferative): Leukaemias, Aplastic anemia, Pure red cell aplasia - > 2% (hyperproliferative): Haemorrhage, Haemolytic anaemias - **MCV > 100**: Macrocytic anemia - Megalocytes and segmented neutrophils on peripheral smear - Present: Megaloblastic: Vitamin B12 and/or Folate deficiency: Drug-induced - Absent: Non-megaloblastic: Alcohol abuse, Myelodysplastic syndrome, Liver disease, Congenital bone marrow failure syndromes ## What is Polycythemia? - It is a condition where the RBC count is high and 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 - **Elevated hemoglobin or hematocrit** - **Elevated red cell mass:** - **O2 saturation**: - > 93%: JAK2V617F - < 93%: Hypoxic erythrocytosis - **Red cell mass and plasma volume measurements**: Both normal: Polycythemia vera - **Normal red cell mass**: Decreased plasma volume: Tobacco use, Androgens, Diuretics, Pheochromocytoma - **Normal or low**: Polycythemia vera, EPO-receptor mutation, Renal disease, Tumors, High-affinity hemoglobins - **Elevated**: Renal disease, Tumors, VHL mutation, High-affinity hemoglobins ## LEUKOPENIA - **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 - **Table 4. Selected Conditions Associated with Elevations in Certain White Blood Cell Types** - **White blood cell line:** - 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 ## Low Platelets - **Thrombocytopenia** ## THROMBOCYTOPENIA - **Platelet Count versus Risk of Hemorrhage** - **Platelet Count**: - > 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 ## THROMBOCYTOPENIA - **Table 2. Recommended physical exercises and corresponding cutoff platelet values for patients with thrombocytopenia based on our literature review.** - **Platelet counts**: - <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. ## THROMBOCYTOPENIA - **Causes of Thrombocytopenia** - **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 ## CAUSES OF THROMBOCYTOSIS - **SIGO FACE** - **Acute or chronic bleeding:** - **Oncological diseases:** - **Infectious diseases:** - **Extensive surgery:** - **Splenectomy:** - **Fracture of large bones (femur, humerus, pelvic bones):** - **Chronic inflammation (colitis, vasculitis, arthritis):** - **The use of glucocorticosteroids:** ## THROMBOCYTOSIS - **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 - **X-linked recessive** - **Deficiency in Factor VIII** - **Causes** - Inherited - Spontaneous mutation - Development of antibodies to Factor VIII ## CAUSES OF HEMOPHILIA - **Father without hemophilia and carrier mother**: - Father: XY - Mother: XX - Son: XY - Daughter: XX - Son: XY - Daughter: XX - **Father with hemophilia and mother who is not a carrier**: - Father: XY - Mother: XX - Son: XY - Daughter: XX - Son: XY - Daughter: XX ## HEMOPHILIA - **Lack of clotting factor reduces the body's ability to control bleeding. ** - Injury occurs - Injury to blood vessel results in bleeding. Vessel constricts and clotting factors are activated - **Normal**: Natural clotting factor helps form a strong platelet plug. A stable fibrin mesh forms a sealed clot over the platelet plug to stop the bleeding. - **Hemophilia**: Lack of natural clotting factor means only a weak platelet plug can form. Incomplete fibrin mesh allows bleeding to continue ## HEMOPHILIA - **Severity**: - **Mild**: 6 - 49% of working factor IX - **Moderate**: 1 - 5% of working factor IX - **Severe**: Less than 1% of working factor IX ## HEMOPHILIA - **Treatment of hemophilia:** - **Walking out of a patient's room should know:** - Type of hemophilia - Patient weight - Factor activity - Severity of bleed - Type of factor - Goal replacement - **Level**: - Mild - Moderate: - **Units of Factor VIII Required**: Weight (kg) x 0.5 x (%. Activity Desired - % Intrinsic Activity*) - **Location**: Soft tissue, Muscle, Hemarthrosis Epistaxis - **Factor Replacement**: Up to 50% - Severe: - **Units of Factor IX Required**: Weight (kg) x 1.0 x (%. Activity Desired - % Intrinsic Activity*) - **Location**: CNS, GI, Neck/Throat - **Factor Replacement**: Up to 100% ## HEMOPHILIA - **Treatment goals:** - Maintain hemostasis - Prevent bleeding episodes - Prevent neuromuscular dysfunction - Prevent disability - Maximize function ## HEMOPHILIA - **Issues in Rehabilitation** - **Joint, Soft tissue, muscle**: Hemarthrosis and hematomas are common and occur spontaneously. - LOM of joint may persist even after bleeding episodes leading to contractures. Hinge joint are not surrounded by protective muscles where ball and socket joints are usually located where there are big muscles protecting them. - Mobilizer muscles may bleed easily since they are at work to produce a movement while stabilizer muscles serves only to hold body against gravity. - **A diagram of a young boy running with a soccer ball.** There are illustrations of multiple joints in the boy's body. The illustrations are of the shoulder, elbow, wrist, hip, knee, and ankle. All the joints are red, indicating inflammation. The boy is in the middle of a run, and the soccer ball is at his feet. ## HEMOPHILIA - 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 - Start with isometrics - Pain-free session - Every session is unique - Consider functional training - Proprioception training ## CANCER - Pathologic process characterized by dysregulated cell growth and systemic spread - All tissue types have neoplastic potential and can be cancerous - Tissues distinguished by rapid cell turnover hormone sensitivity and regular exposure to mutagens have higher rate of malignant transformation - **Disease consideration**: - Staging - Metastasis - Prognosis ## CANCER STAGING - **A diagram of five boxes with purple fill arranged in a line, each box representing a stage of cancer. ** - **Stage 0**: Carcinoma in situ - Early form - **Stage I**: Localized - **Stage II**: Early Locally advanced - **Stage III**: Late Locally Advanced - **Stage IV**: Metastasized ## TMN - 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 - **A diagram of two boxes with a line separating the boxes**. The boxes on the left and right are labelled "Benign" and "Malignant," respectively. The line between the boxes is split into three sections, "Low-grade malignant," "Locally agressive," and "Borderline." - **Benign**: - Slow growth rate - No infiltration - No metastasis - High patient survival rates after successful surgical removal - **Low-grade malignant, Locally agressive, 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 - **A circle with six segments, each representing a hallmark of cancer.** The center of the circle is filled with cancerous-looking cells. - **Each segment of the circle contains the name of a hallmark:** - **Evading apoptosis**: - **Sustained angiogenesis**: - **Limitless replicative potential**: - **Self-sufficiency in growth signals**: - **Insensitivity to antigrowth signals**: - **Tissue invasion and metastasis**: - **Hanahan & Weinberg, Cell 2000.** ## 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. ## PHASES OF CANCER - **Temporization**: - In patient with recurrence not deemed curable, goal is to control disease and symptoms and prevent or address disability. - **Palliation**: - Focused on patient's comfort. - **Goals:** - Preserve community integration. - Support and educate caregiver. - Maintain functional autonomy. ## REHABILITATION PLANNING - **Anticipation of problem:** - Likely metastasis. - Respond to treatment . - **Cumulative toxicities from treatment:** - **Life expectancy:** - **Symptom-oriented vs disease-modifying treatment strategy** ## BOX 29-1 - **Rehabilitation Priorities During Cancer Phases**: - **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 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. ## BOX 29-3 - **Considerations in Cancer Pain Management**: - 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. - **A diagram of a person sitting in a slump with a speech bubble above them showing "Battling Fatigue."** The speech bubble is filled with a blue circle segmented into two parts with the segments showing "40% of people struggle with fatigue related to cancer." ## CRITERIA FOR CANCER RELATED FATIGUE - **DIPPED SLID**: - 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**: ## BOX 29-2 - **Reversible Sources of Cancer Fatigue**: - 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 that are 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 affects and/or destroy normal tissues. - Triggered during early stages of CA. - 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. ## IMPAIRMENT IN CANCER - **TUMOR EFFECTS - BRAIN TUMOR**: - Most commonly metastasis from lung cancer. - Headache > Mental Disturbance > Focal Weakness > Gait Ataxia > Seizure. - Corticosteroid first line of treatment. - Dexamethasone is the drug of choice. - Untreated patients have median survival rate of 1 to 2 months. ## IMPAIRMENT IN CANCER - **TUMOR EFFECTS - BONE METASTASIS**: - Most common site of metastatic spread. - Bisphosphonates for bone 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. ## IMPAIRMENT IN CANCER - **TUMOR EFFECTS - 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. ## IMPAIRMENT IN CANCER - **TUMOR EFFECTS - BRACHIAL PLEXOPATHY**: - Most common source is from lungs and breast CA. - 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 whether expected or unexpected. - Injury to the recurrent laryngeal nerve in thyroid cancer ## IMPAIRMENT IN CANCER - **CANCER TREATMENT - RADIATION THERAPY**: - **Timing**: - Acute < 4 weeks post RT - Early 1-6 months post RT - Late > 6 months post RT - Adverse effects mainly due to affected normal tissues. - Complications from radiation therapy depends on the site treated. ## IMPAIRMENT IN CANCER - **RADIATION INDUCED MYELOPATHY**: - **Early-onset myelopathy**: - Peak at 4-6 months. - Resolves within 9 months. - Clinical onset is marked by paresthesia that radiate from 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 symptom usually begins with LE paresthesia followed by sphincter dysfunction and weakness. ## Radiation-associated brain injury - **A diagram of a box with four sections, each representing a different stage of radiation-associated brain injury**. The sections of the box are labelled "Days," "Weeks," "Months," and "Years." Each of the sections has a box inside it, "acute", "early delayed", "late delayed", and an empty box. - **Days (Acute)** : Transient edema characterized by drowsiness, headache, nausea, vomiting, worsening of pre-existing focal neurologic symptoms - **Weeks (Early Delayed)**: Transient demyelination characterized by headache, somnolence, fatigability, attention deficits, and short-term memory loss - **Months (Late Delayed)**: Irreversible and progressive necrosis, diffuse white matter injury, and leukoencephalopathy characterized by cognitive dysfunction, ataxia, confusion, dysarthria, seizures, dementia, and death ## IMPAIRMENT IN CANCER - **CANCER TREATMENT - 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. ## IMPAIRMENT IN CANCER - **CANCER TREATMENT - CHEMOTHERAPY**: - **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, 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. ## IMPAIRMENT IN CANCER - **CANCER TREATMENT - LYMPHEDEMA**: - Damaged lymphatics either from surgical removal or from radiotherapy. - Treatment is complex decongestive therapy (CDT). - **Reductive phase**: Decrease lymphedema volume - **Maintenance phase**: Teach self-management techniques. ## REDUCTIVE PHASE - **45 minutes of manual lymphatic drainage (MLD):** 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.