Hematological Conditions
Congenital: Hemophilia & Thalassemia
Comprehensive nursing notes for student education
Introduction to Congenital Hematological Disorders
Congenital hematological disorders are inherited blood conditions that affect the production or function of blood components. This set of notes focuses on two major congenital blood disorders: Hemophilia and Thalassemia.
Congenital Hematological Disorders Overview
Hemophilia
Clotting factor deficiency
X-linked recessive inheritance
Bleeding disorder
Thalassemia
Hemoglobin production disorder
Autosomal recessive inheritance
Anemia
Hemophilia
Definition: Hemophilia is an X-linked recessive bleeding disorder characterized by deficiency in clotting factors, primarily Factor VIII (Hemophilia A) or Factor IX (Hemophilia B), resulting in prolonged bleeding and spontaneous hemorrhages.
Pathophysiology
The coagulation cascade involves a series of enzymatic reactions that ultimately lead to the formation of a stable fibrin clot. In hemophilia, the absence or deficiency of specific clotting factors disrupts this cascade.
Normal Clotting Cascade vs. Hemophilia
Normal Clotting
- Vessel injury exposes collagen
- Platelets adhere and become activated
- Coagulation cascade activates
- Factor VIII/IX participate in cascade
- Thrombin generated
- Fibrinogen converted to fibrin
- Stable clot forms
Hemophilia
- Vessel injury exposes collagen
- Platelets adhere and become activated
- Coagulation cascade activates
- Factor VIII/IX deficient or absent
- Reduced thrombin generation
- Inefficient fibrin formation
- Unstable clot forms
Coagulation cascade showing where hemophilia A and B cause disruptions
Types of Hemophilia
| Type | Deficient Factor | Frequency | Inheritance | Also Known As |
|---|---|---|---|---|
| Hemophilia A | Factor VIII | 1 in 5,000-10,000 male births | X-linked recessive | Classic Hemophilia |
| Hemophilia B | Factor IX | 1 in 30,000 male births | X-linked recessive | Christmas Disease |
| Hemophilia C | Factor XI | Rare | Autosomal recessive | Rosenthal Syndrome |
Severity Classification
| Severity | Factor Level | Clinical Presentation |
|---|---|---|
| Mild | 5-40% of normal | Bleeding with major trauma or surgery |
| Moderate | 1-5% of normal | Bleeding with minor trauma; occasional spontaneous bleeding |
| Severe | <1% of normal | Spontaneous bleeding; bleeding into joints and muscles |
Clinical Manifestations
Common Bleeding Sites
- Hemarthrosis (joint bleeding) – knees, elbows, ankles
- Muscle hematomas
- Mucosal bleeding (mouth, nose, GI tract)
- Intracranial hemorrhage (life-threatening)
- Hematuria
- Prolonged bleeding after injury or surgery
Complications
- Chronic arthropathy (joint damage)
- Joint deformities and disability
- Inhibitor development (antibodies against treatment factors)
- Chronic pain
- Neurological damage (if CNS bleeding)
- Compartment syndrome from large muscle bleeds
HEMARTHROSIS Mnemonic for Hemophilia Joint Bleeding
- Hot to touch
- Edema (swelling)
- Mobility decreased
- Acute pain
- Redness
- Tenderness
- Hold in flexion (patient keeps joint bent)
- Range of motion limited
- Obvious joint effusion
- Stiffness
- Inflammation
- Spasm of muscles around joint
Diagnosis
- Laboratory Tests:
- Factor VIII or IX activity level (decreased)
- Prolonged aPTT (activated partial thromboplastin time)
- Normal PT (prothrombin time)
- Normal platelet count
- Normal bleeding time
- Imaging:
- X-rays of affected joints (for chronic changes)
- MRI to evaluate joint and soft tissue bleeding
- CT scan for suspected intracranial bleeding
- Genetic Testing:
- Mutation analysis of F8 (Hemophilia A) or F9 (Hemophilia B) genes
- Carrier detection in female relatives
- Prenatal diagnosis
Treatment Approaches
Factor Replacement Therapy
- Recombinant factor concentrates (preferred)
- Plasma-derived factor concentrates
- On-demand therapy (given when bleeding occurs)
- Prophylactic therapy (regular infusions to prevent bleeding)
- Home administration programs
Newer Therapeutic Approaches
- Extended half-life factor products
- Emicizumab (Hemlibra) – mimics factor VIII function
- Non-factor replacement therapies
- Gene therapy trials
- Bypassing agents for patients with inhibitors (FEIBA, NovoSeven)
Supportive Therapies
- Desmopressin (DDAVP) for mild Hemophilia A
- Antifibrinolytics (tranexamic acid, aminocaproic acid)
- Pain management
- Physical therapy for joint rehabilitation
- Orthopedic interventions for joint damage
Thalassemia
Definition: Thalassemia is a group of inherited autosomal recessive blood disorders characterized by reduced or abnormal synthesis of one or more hemoglobin chains, leading to various degrees of anemia and ineffective erythropoiesis.
Pathophysiology
Thalassemia results from mutations in genes that code for hemoglobin chains. Normal adult hemoglobin (HbA) consists of two alpha and two beta chains (α₂β₂). The imbalance in globin chain production leads to ineffective erythropoiesis, hemolysis, and anemia.
Pathophysiological Sequence in Thalassemia
- Genetic mutations affect α or β globin chain production
- Imbalanced globin chain synthesis occurs
- Excess unpaired chains precipitate in erythroid precursors
- Premature erythroid cell death in bone marrow (ineffective erythropoiesis)
- Surviving red cells have shortened lifespan (hemolysis)
- Chronic anemia develops
- Compensatory erythropoiesis and bone marrow expansion occurs
- Iron overload from increased absorption and repeated transfusions
Types of Thalassemia
| Type | Affected Chain | Genetics | Severity | Clinical Features |
|---|---|---|---|---|
| Alpha Thalassemia | ||||
| Silent Carrier (α-thalassemia minima) |
Alpha | 1 of 4 α genes deleted | Asymptomatic | No anemia, normal red cell indices |
| Alpha Thalassemia Trait (α-thalassemia minor) |
Alpha | 2 of 4 α genes deleted | Mild | Mild microcytic anemia, no clinical symptoms |
| Hemoglobin H Disease | Alpha | 3 of 4 α genes deleted | Moderate | Moderate hemolytic anemia, splenomegaly, occasionally transfusion-dependent |
| Hydrops Fetalis (Hb Bart’s) |
Alpha | All 4 α genes deleted | Very severe | Usually fatal in utero or shortly after birth |
| Beta Thalassemia | ||||
| Beta Thalassemia Minor (β-thalassemia trait) |
Beta | 1 β gene mutation | Mild | Mild microcytic anemia, asymptomatic |
| Beta Thalassemia Intermedia | Beta | 2 β gene mutations (mild) | Moderate | Moderate anemia, occasionally transfusion-dependent, splenomegaly, bone changes |
| Beta Thalassemia Major (Cooley’s Anemia) |
Beta | 2 β gene mutations (severe) | Severe | Severe anemia, transfusion-dependent, growth retardation, skeletal changes, iron overload |
Clinical Manifestations
Beta Thalassemia Major (Cooley’s Anemia)
- Severe anemia (Hb 3-7 g/dL without transfusions)
- Failure to thrive and growth retardation
- Jaundice and pallor
- Hepatosplenomegaly
- Skeletal changes (chipmunk facies, frontal bossing)
- Pathologic fractures
- Delayed puberty
- Iron overload complications (heart failure, arrhythmias, diabetes, hypothyroidism)
Thalassemia Intermedia & Minor
- Intermedia:
- Moderate anemia (Hb 7-10 g/dL)
- Splenomegaly
- Milder skeletal changes
- May require occasional transfusions
- Growth retardation possible
- Minor (Trait):
- Usually asymptomatic
- Mild microcytic anemia
- Often mistaken for iron deficiency
THALASSEMIA Mnemonic for Clinical Features
- Transfusion-dependent anemia
- Hepatosplenomegaly (enlarged liver and spleen)
- Abnormal facial features (chipmunk facies)
- Leg ulcers in some patients
- Abnormal hemoglobin production
- Skeletal changes (bone marrow expansion)
- Secondary hemochromatosis (iron overload)
- Endocrine dysfunction (from iron deposition)
- Microcytic, hypochromic anemia
- Iron chelation therapy needed
- Autosomal recessive inheritance
Diagnosis
- Complete Blood Count (CBC):
- Decreased hemoglobin and hematocrit
- Microcytic (low MCV), hypochromic (low MCH) anemia
- Elevated red cell count (despite anemia)
- Increased RDW (red cell distribution width)
- Peripheral Blood Smear:
- Microcytosis, hypochromia
- Target cells (codocytes)
- Basophilic stippling
- Nucleated RBCs
- Anisocytosis and poikilocytosis
- Hemoglobin Analysis:
- Hemoglobin electrophoresis
- High Performance Liquid Chromatography (HPLC)
- β-thalassemia: Elevated HbF and HbA₂, reduced or absent HbA
- α-thalassemia: Hb H inclusion bodies (in Hb H disease)
- Additional Tests:
- Serum iron, ferritin, TIBC (to differentiate from iron deficiency)
- Genetic testing for specific mutations
- Family studies
- Prenatal diagnosis (chorionic villus sampling, amniocentesis)
Treatment Approaches
Blood Transfusion Therapy
- Regular transfusions (every 3-4 weeks)
- Goal: maintain pre-transfusion Hb > 9-10 g/dL
- Leukocyte-reduced packed RBCs
- Extended cross-matching recommended
- Monitoring for transfusion reactions
Iron Chelation Therapy
- Deferoxamine (subcutaneous or IV infusion)
- Deferasirox (oral, once daily)
- Deferiprone (oral, three times daily)
- Monitoring of serum ferritin levels
- T2* MRI for cardiac/liver iron assessment
Additional Management
- Splenectomy (for hypersplenism)
- Folic acid supplementation
- Hydroxyurea (to increase HbF production)
- Management of endocrine complications
- Calcium and vitamin D for bone health
- Hepatitis B vaccination
- Psychological support
Curative Approaches
- Hematopoietic stem cell transplantation (HSCT)
- Only curative treatment currently available
- Best results when performed before iron overload complications
- HLA-matched sibling donor preferred
- Gene therapy (emerging treatment)
- Lentiviral vector-mediated gene transfer
- CRISPR-Cas9 gene editing
Comparison: Hemophilia vs. Thalassemia
| Feature | Hemophilia | Thalassemia |
|---|---|---|
| Primary Defect | Clotting factor deficiency | Abnormal hemoglobin chain synthesis |
| Inheritance Pattern | X-linked recessive (primarily affects males) | Autosomal recessive (affects males and females equally) |
| Primary Clinical Manifestation | Bleeding tendency | Anemia |
| Characteristic Lab Finding | Prolonged aPTT, normal PT | Microcytic, hypochromic anemia |
| Ethnic Distribution | All populations | Mediterranean, Middle Eastern, Asian, African populations |
| Main Treatment | Factor replacement therapy | Blood transfusions + iron chelation |
| Curative Therapy | Gene therapy (experimental) | Hematopoietic stem cell transplantation |
| Major Complications | Joint deformities, inhibitor development | Iron overload, endocrinopathies, heart disease |
Nursing Care Considerations
Nursing Care for Hemophilia
Assessment
- Monitor for signs of bleeding (visible and occult)
- Assess for joint pain, swelling, or limited mobility
- Evaluate pain levels and effectiveness of pain management
- Screen for inhibitor development
- Assess psychosocial impact of chronic condition
Nursing Diagnoses
- Risk for Bleeding related to clotting factor deficiency
- Chronic Pain related to joint damage
- Impaired Physical Mobility related to hemarthrosis
- Risk for Infection related to frequent factor infusions
- Deficient Knowledge related to home management of disorder
Interventions
- Administer factor replacement therapy per protocol
- Teach proper venipuncture technique for self-administration
- Apply cold compresses to acute bleeds (RICE: Rest, Ice, Compression, Elevation)
- Implement bleeding precautions:
- Use soft toothbrush
- Electric razors instead of blades
- Avoid IM injections
- Assist with pain management techniques
- Coordinate physical therapy consultations
Patient Education
- Recognition of bleeding episodes
- Home factor administration techniques
- Maintaining factor treatment record
- Appropriate physical activities and safety precautions
- Importance of medical alert identification
- Avoiding NSAIDs and aspirin
- Genetic counseling referrals
Nursing Care for Thalassemia
Assessment
- Monitor for signs of anemia (fatigue, pallor, tachycardia)
- Assess growth and development in children
- Evaluate for signs of iron overload
- Monitor vital signs during transfusions
- Assess for transfusion reactions
- Evaluate endocrine function
Nursing Diagnoses
- Activity Intolerance related to decreased oxygen-carrying capacity
- Risk for Infection related to chronic transfusion therapy
- Imbalanced Nutrition related to increased metabolic demands
- Disturbed Body Image related to physical changes
- Risk for Impaired Skin Integrity related to chelation therapy
Interventions
- Administer blood transfusions as prescribed
- Monitor for transfusion reactions
- Administer iron chelation therapy per protocol
- Monitor chelation therapy side effects
- Support adequate nutrition and hydration
- Implement energy conservation techniques
- Monitor growth patterns in children
Patient Education
- Importance of regular transfusions and chelation therapy
- Administration of chelation therapy at home
- Managing side effects of chelation
- Recognition of transfusion reactions
- Nutritional guidance (avoiding excess iron-rich foods)
- Importance of regular follow-up appointments
- Genetic counseling referrals
Helpful Mnemonics for Learning
CLOT Mnemonic for Hemophilia Assessment
- Coagulation factors (level and inhibitors)
- Locations of bleeding (joints, muscles, internal)
- Onset and duration of bleeding episodes
- Treatment history and response
IRON CHAINS for Thalassemia Major Care
- Iron overload monitoring and management
- Regular transfusion schedule
- Organ function assessment (heart, liver, endocrine)
- Nutritional support
- Chelation therapy adherence
- Hematologic parameters monitoring
- Activity tolerance evaluation
- Infection prevention
- Normal growth and development assessment
- Support system engagement
Key Nursing Priorities Mind Map
Assessment
Baseline & Ongoing
Administration
Medications & Treatments
Education
Patient & Family
Support
Psychosocial & Emotional
Coordination
Multidisciplinary Care