Bhalani Medicine Pg 122-131

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Questions and Answers

What is the desired factor VIII level for treating a central nervous system hemorrhage?

50-100% (correct)

30-50%

30-100%

~50%

Immune tolerance induction (ITI) is an ineffective strategy for eradication of factor VIII inhibitors.

False

What monoclonal antibody is used as a substitute for factor VIII in patients with inhibitors?

Emicizumab

Chronic complications of receiving factor VIII therapy can include _____ infection.

HIV and HCV Signup and view all the answers

Match the types of therapy for hemophilia with their descriptions:

Gene therapy = A technique to treat genetic disorders by correcting defective genes Concizumab = A monoclonal antibody directed against tissue factor pathway inhibitor Signup and view all the answers

Which treatment option is indicated for patients with ITP who are unresponsive to steroids?

Rh(D) Immune Globulin (anti-D) Signup and view all the answers

TPO Mimetic Drugs can be administered intravenously.

False Signup and view all the answers

What is the effective dose range for High Dose Corticosteroids in treating ITP?

1-2 g/kg Signup and view all the answers

High Dose Corticosteroids are typically effective for a duration of ______.

3-4 weeks Signup and view all the answers

Match each treatment with its corresponding indication:

High Dose Corticosteroids = Patients with intracranial bleeding Immunosuppressive Therapy = Refractory cases unresponsive to therapies Intravenous Immunoglobulin (IgG) = Acute situations prior to surgery Platelet Transfusions = Life-threatening bleeding situations Signup and view all the answers

Which option describes a common side effect of both Intravenous Immunoglobulin (IgG) and High Dose Corticosteroids?

Nausea Signup and view all the answers

Immunosuppressive therapy is utilized for all patients with ITP.

False Signup and view all the answers

The maximum dose of intravenous methylprednisolone for emergency treatment is ______.

1 g Signup and view all the answers

What is the primary cell type in Hodgkin lymphoma?

Reed-Sternberg cells Signup and view all the answers

Hodgkin lymphoma is primarily associated with T-cell lineage.

False Signup and view all the answers

What are the two peak age ranges for Hodgkin lymphoma incidence?

15-35 years and 45-75 years Signup and view all the answers

Reed-Sternberg cells in classical Hodgkin lymphoma are characterized by being CD15+ and CD30+; however, in lymphocyte predominance Hodgkin lymphoma, these cells are CD15- and CD30-.

CD15+, CD30+; CD15-, CD30- Signup and view all the answers

Match the following types of Hodgkin lymphoma with their characteristics:

Nodular sclerosis = Most common type in the US Mixed cellularity = Most common type in India Lymphocyte-rich = Characterized by high lymphocyte count Lymphocyte depletion = Associated with poorer prognosis Signup and view all the answers

What is characterized by pancytopenia and hypocellular bone marrow?

Aplastic Anemia Signup and view all the answers

Aplastic anemia often presents with elevated leukocyte levels.

False Signup and view all the answers

What are the three types of blood cells that are reduced in aplastic anemia?

Red blood cells, white blood cells, platelets Signup and view all the answers

In severe aplastic anemia, the neutrophil count is less than ______ x 10^9/L.

0.5 Signup and view all the answers

Match the following features with their corresponding blood cell deficiencies:

Anemia = Fatigue and weakness Neutropenia = Frequent infections Thrombocytopenia = Bleeding manifestations Reticulocytopenia = Decreased immature red blood cells Signup and view all the answers

Which condition is a potential inherited form of aplastic anemia?

Fanconi's Anemia Signup and view all the answers

Pancytopenia is a decrease in all three major blood cell types.

True Signup and view all the answers

What are some common bleeding manifestations seen in thrombocytopenia?

Petechiae, bruises, epistaxis Signup and view all the answers

What is the normal range for the NAP/LAP score?

40-100 Signup and view all the answers

Elevated serum vitamin B12 levels are due to a decrease in granulocyte production.

False Signup and view all the answers

What is the first-line treatment for Chronic Myeloid Leukemia?

Imatinib mesylate Signup and view all the answers

Chronic Myeloid Leukemia can progress to a more aggressive phase called ____________.

blast crisis Signup and view all the answers

Match the following drugs with their respective dosages.

Imatinib mesylate = 400 mg/day Hydroxyurea = 0.5-2.0 g/day Melphalan = 4-12 mg/day Busulphan = 4 mg/day Signup and view all the answers

Which of the following is NOT a side effect of Imatinib mesylate?

Flu-like syndrome Signup and view all the answers

Bone marrow transplantation is not considered for patients who respond to second-line TKIs.

True Signup and view all the answers

What is one of the main complications of Chronic Myeloid Leukemia?

Fatigue due to anemia Signup and view all the answers

The drug ____________ is most effective during the accelerated phase of CML.

Hydroxyurea Signup and view all the answers

What percentage of patients may achieve a cure rate with a stem cell transplantation if done in the early chronic stable phase?

70% Signup and view all the answers

What is the main criterion for the Revised FAB Classification of Acute Leukemias?

The number of blasts must be 30% or more in the bone marrow Signup and view all the answers

Both the FAB and WHO classifications use the same percentage of blasts for diagnosis.

False Signup and view all the answers

Name one type of Acute Myeloblastic Leukemia (AML).

M3: Acute promyelocytic leukemia Signup and view all the answers

In the WHO Classification, B-cell lymphoblastic leukemia/lymphoma can have _____ abnormalities.

recurrent genetic Signup and view all the answers

Match the following types of leukemia with their corresponding classification:

CML = Chronic myeloid leukemia ALL = Acute lymphoblastic leukemia APL = Acute promyelocytic leukemia CLL = Chronic lymphocytic leukemia Signup and view all the answers

Which subtype corresponds to 'L3' in the classification of Acute Lymphoblastic Leukemia?

Large cells with prominent nucleoli and abundant vacuolated cytoplasm Signup and view all the answers

Acute monocytic leukemia is classified as M5 in the Revised FAB Classification.

True Signup and view all the answers

What is the main focus of the WHO classification of leukemias?

Morphology, cytochemistry, cytogenetics, molecular genetics, and clinical features. Signup and view all the answers

Chronic lymphocytic leukemia is abbreviated as _____ .

CLL Signup and view all the answers

Which of the following subtypes is NOT a type of Acute Myeloblastic Leukemia?

M2: Chronic myeloid leukemia Signup and view all the answers

What classification method is used for clinical staging of Hodgkin lymphoma?

Cotswolds modification of the Ann Arbor Classification Signup and view all the answers

Lymphopenia is associated with a good prognosis in Hodgkin lymphoma.

False Signup and view all the answers

What blood test might show elevated levels indicating bone marrow or liver involvement?

Serum Alkaline Phosphatase Signup and view all the answers

The chemotherapy regimen ABVD includes Doxorubicin, Bleomycin, Vinblastine, and __________.

Dacarbazine Signup and view all the answers

Match the following stage categories of Hodgkin lymphoma with their respective treatment options:

IA or IIA, no bulky disease = ABVD × 4 or ABVD × 2 + IRRT IB, IIB, or any stage III or IV = ABVD until 2 cycles past complete remission Bulky disease, any stage = BEACOPP escalated Signup and view all the answers

Which of the following is a B symptom often associated with Hodgkin lymphoma?

Fever Signup and view all the answers

Positron Emission Tomography (PET) can be used for staging Hodgkin lymphoma.

True Signup and view all the answers

What is indicated in the staging of advanced Hodgkin lymphoma (stages III and IV)?

Bone marrow trephine and aspirate Signup and view all the answers

Eosinophilia is observed in about __________ percent of Hodgkin lymphoma patients.

20 Signup and view all the answers

Which of the following factors is NOT considered an adverse factor in Hodgkin lymphoma prognosis?

Female sex Signup and view all the answers

What is the most common hereditary X-linked recessive disorder?

Hemophilia A Signup and view all the answers

Females can be hemophilic if they inherit an affected X chromosome from an affected father and a carrier mother.

True Signup and view all the answers

What is the incidence of Hemophilia A in males?

1 in 10,000 Signup and view all the answers

The ____ of hemophilia A is primarily due to a deficiency of factor VIII.

etiology Signup and view all the answers

Which clinical feature is generally not observed in hemophilia?

Petechiae Signup and view all the answers

Match the categories of hemophilia severity with their factor VIII levels:

Mild = 6-30% of normal Moderate = 1-5% of normal Severe = ≤1% of normal Signup and view all the answers

The bleeding time in patients with Hemophilia A is prolonged.

False Signup and view all the answers

What is one indication for replacement therapy in Hemophilia A?

Early treatment of spontaneous bleeding Signup and view all the answers

The formula to calculate the dose of Factor VIII is: Dose = Desired factor level (percentage) × body weight (kg) × ____

0.5 Signup and view all the answers

Which of the following is NOT a common site for bleeding in Hemophilia A?

Forearm Signup and view all the answers

What is a common cause of increased platelet destruction in thrombocytopenia?

Idiopathic thrombocytopenic purpura (ITP) Signup and view all the answers

Secondary immune thrombocytopenic purpura is less common than primary immune thrombocytopenic purpura.

True Signup and view all the answers

What is the platelet count threshold for diagnosing thrombocytopenia?

150,000/µL Signup and view all the answers

The autoimmune disorder characterized by increased destruction of platelets is called _____________.

idiopathic thrombocytopenic purpura Signup and view all the answers

Match the types of ITP with their characteristics:

Acute, = More common in children Chronic, = Persistence over 6 months, more common in adults Signup and view all the answers

Which of the following is NOT a cause of decreased platelet production?

Thyroid disease Signup and view all the answers

Splenomegaly is a common feature observed in primary ITP.

False Signup and view all the answers

Name one infection that can result in drug-induced thrombocytopenia.

HIV Signup and view all the answers

Increased platelet sequestration is commonly due to _____________.

hypersplenism Signup and view all the answers

Which of the following is a clinical feature of ITP?

Intracranial hemorrhage Signup and view all the answers

What genetic abnormality is primarily associated with Chronic Myeloid Leukemia?

Philadelphia chromosome Signup and view all the answers

CML has a sudden onset that is easy to recognize.

False Signup and view all the answers

Name one symptom associated with massive splenomegaly in CML.

Fullness of the abdomen Signup and view all the answers

The BCR-ABL1 fusion gene results from a translocation between chromosomes 9 and ______.

22 Signup and view all the answers

Match the following phases of CML with their characteristics:

Chronic stable phase = Lasts 3-5 years without treatment Accelerated phase = Becomes more aggressive, lasts a few months Blast crisis phase = Similar to acute leukemia with poor prognosis Signup and view all the answers

What is the typical age range for the diagnosis of Chronic Myeloid Leukemia?

40-60 years old Signup and view all the answers

In CML, patients often experience prolonged painful erections due to leukostasis.

True Signup and view all the answers

What is a common peripheral blood finding in Chronic Myeloid Leukemia?

Left shift (immature granulocytes) Signup and view all the answers

In CML, hemoglobin levels are usually below ______ g/dL.

11 Signup and view all the answers

What percentage of CML cases show the Philadelphia chromosome?

Over 95% Signup and view all the answers

Study Notes

Factor VIII Doses for Hemorrhage Treatment

Hemarthrosis requires a factor VIII level of 30-50% of normal, achieved with ~25 U/kg body weight, every 12-24 hours for 1-2 days.
Superficial intramuscular hematoma requires a similar factor VIII level, dose, and frequency to hemarthrosis.
Gastrointestinal bleeding needs ~50% of normal factor VIII, with ~25 U/kg body weight every 12 hours for 7-10 days.
Epistaxis and oral mucosa bleeding both require factor VIII levels of 30-50%, achieved with ~25 U/kg body weight every 12 hours until resolution.
Hematuria requires a higher factor VIII level of 30-100%, reached with ~25-50 U/kg body weight every 12 hours until resolution.
Central nervous system, retropharyngeal, and retroperitoneal bleeding all necessitate factor VIII levels of 50-100%, achieved with 50 U/kg body weight every 12 hours for at least 7-10 days.

Factor VIII Therapy Complications

Around 15% of patients receiving factor VIII develop inhibitory antibodies.
Immune tolerance induction (ITI) with steroids or immunosuppressants is the most effective treatment for factor VIII inhibitors.
Emicizumab, a bifunctional monoclonal antibody, can substitute for factor VIII in individuals with inhibitors.
Antibodies to AHG may develop in non-hemophiliacs with immunological disorders like systemic lupus erythematosus.
Chronic complications of factor VIII therapy include arthropathy, HIV and HCV infection, and inhibitor development.

Hemophilia Preventive Therapy

Gene therapy holds potential for preventing hemophilia.
Concizumab, a monoclonal antibody targeting tissue factor pathway inhibitor, is another preventive strategy.

Immune Thrombocytopenia (ITP) Treatment Options

High-dose corticosteroids: Used in acute situations like surgery or childbirth, intracranial bleeding, or when other therapies are contraindicated.
Intravenous Immunoglobulin (IgG): Effective in acute situations, intracranial bleeding, and when corticosteroids and splenectomy are unsuitable.
Rh(D) Immune Globulin (anti-D): Useful for patients unresponsive to steroids, potentially as a step before splenectomy. Only effective in Rh-positive patients.
Immunosuppressive Therapy: Employed in refractory cases unresponsive to corticosteroids and splenectomy, or when other options are unsuitable.
Plasmapheresis: A rapid, temporary measure to remove antibodies from the plasma used in emergencies.
TPO Mimetic Drugs: Eltrombopag or romiplostim can increase platelet production.
Specific Immunomodulatory Monoclonal Antibodies: Rituximab can target specific immune cells.
Danazol and Dapsone: Androgenic and sulfone drugs, respectively, have been investigated for ITP.
Platelet Transfusions: Reserved for severe hemorrhages when emergency splenectomy is warranted.
Emergency Treatment: Intravenous methylprednisolone, platelet transfusion, and IV immunoglobulin are administered for life-threatening bleeding.

Leukemia Classification

General/Traditional Classification: Categorizes leukemias based on cell appearance and evolution rate.
Revised FAB Classification of Acute Leukemias: Utilizes morphological, cytochemical, immunophenotypic, cytogenetic, and molecular genetic parameters. Requires a blast count of 30% or more in bone marrow.
WHO Classification (2016): Incorporates morphology, cytochemistry, cytogenetics, molecular genetics, and clinical features. Requires a blast count greater than 20% in bone marrow.

Traditional Classification of Leukemia

Acute leukemias: AML (Acute Myeloblastic/Myelocytic Leukemia) and ALL (Acute Lymphoblastic/Lymphocytic Leukemia).
Chronic leukemias: CML (Chronic Myeloid Leukemia) and CLL (Chronic Lymphocytic Leukemia).

Revised FAB Classification of Acute Leukemias

AML types: M0 (Minimally Differentiated AML), M1 (AML Without Differentiation), M2 (AML With Maturation), M3 (Acute Promyelocytic Leukemia), M4 (Acute Myelomonocytic Leukemia), M5 (Acute Monocytic Leukemia), M6 (Acute Erythroleukemia), M7 (Acute Megakaryocytic Leukemia).
ALL types: L1 (Small cells with homogeneous nuclear chromatin), L2 (Large, heterogeneous cells with variable cytoplasm), L3 (Large, homogeneous cells with prominent nucleoli and basophilic cytoplasm).

WHO Classification of Acute Lymphoblastic Leukemia

B-cell lymphoblastic leukemia/lymphoma: Unspecified, with recurrent genetic abnormalities (hypodiploidy, hyperdiploidy, t(9;22), t(v;11q23), t(12;21), t(1;19), t(5;14), iAMP21, BCR-ABL1-like ALL).
T-cell lymphoblastic leukemia/lymphomas: Early T-cell precursor lymphoblastic leukemia.

WHO Classification of Acute Myeloid Leukemia

AML with recurrent genetic abnormalities: M2 (favorable), M4eo (favorable), M3, M3v (intermediate), M4, M5 (intermediate), unspecified (poor, variable).
AML not otherwise specified: M0 (intermediate), M1 (intermediate), M2 (intermediate), M4 (intermediate), M5a, M5b (intermediate), M6a, M6b (intermediate), M7 (intermediate), unspecified (poor, variable).

Chronic Myeloid Leukemia (CML)

Decreased NAP/LAP score: Usually below 20 in most patients, helpful in differentiating CML from leukemoid reaction.
Biochemical findings: Increased serum LDH, uric acid, and alkaline phosphatase. Elevated serum vitamin B12 due to binding protein production by granulocytes. Thrombocytosis can spuriously increase serum potassium levels. Blood sugar may be falsely decreased due to glucose uptake by leukocytes.

Treatment and Complications of Chronic Myeloid Leukemia

Goal of Therapy: Achieve complete molecular remission, prolonged, durable, non-neoplastic hematopoiesis, and eradication of residual BCR-ABL1 transcript cells.
Chemotherapy: Imatinib mesylate (first-line), second-generation TKIs if imatinib fails, allogeneic bone marrow transplantation, classical cytotoxic drugs.
Recombinant interferon-α: Used in some cases, can induce remission and control CML, but not effective in accelerated or blast crisis phases.

Accelerated Phase of CML

Occurs after 1-5 years from onset, lasting a few months.
Features: Increasing anemia and white blood cell count, unresponsive to therapy. Splenomegaly. Increased basophil count. Persistent thrombocytopenia or thrombocytosis unresponsive to therapy.
Hydroxyurea is the most effective drug in this phase.

Blast Crisis Phase of CML

Transformation of CML into acute leukemia lasting weeks to months.
Poor prognosis.
Features: Blast cells constitute 20% or more of blood cells (myeloid blast crisis in ~70%, lymphoid in ~30%).
Treatment: Similar to acute leukemia.

Complications of CML

Fatigue due to anemia.
Excessive bleeding due to thrombocytopenia.
Bone pain or joint pain due to bone marrow expansion.
Enlarged spleen.
Vulnerability to infections due to impaired immune system.
Death.

Drug Dosages for CML Treatment

Imatinib mesylate: Induction and maintenance dosage of 300-400 mg/day.
Hydroxyurea: Induction and maintenance dosage of 0.5-2.0 g/day.
Melphalan: Induction dosage of 4-12 mg/day, maintenance dosage of 2-4 mg/day.
Busulphan: Induction dosage of 4 mg/day, maintenance dosage of 2-4 mg/day.

Splenectomy for CML

Indicated to relieve symptoms of massive splenomegaly and repeated splenic infarctions.

Stem Cell Transplantation (SCT) for CML

Indications: Patients under 60 with a suitable donor, those unresponsive to second-line TKIs, or those with accelerated or blast phase.
Best results: Achieved in the early chronic stable phase, often achieving a cure rate of ~70%.
Disadvantages: Risk of complications and death due to graft-versus-host disease (GVHD).

Aplastic Anemia

Characterized by pancytopenia, hypocellular bone marrow (less than 30% cellularity), and no leukemic or abnormal cells in the peripheral blood or bone marrow.

Causes of Aplastic Anemia

Idiopathic (unknown cause): Most common.
Drug-induced: Chemicals, antibiotics, anticonvulsants, heavy metals.
Radiation exposure: High doses of radiation used for cancer treatment.
Viral infections: Hepatitis, Epstein-Barr, cytomegalovirus, HIV.
Autoimmune disorders: Systemic lupus erythematosus, rheumatoid arthritis.
Genetic syndromes: Fanconi's anemia, Bloom syndrome.
Other causes: Pregnancy, pregnancy complications, hypothyroidism.

Clinical Features of Aplastic Anemia

Insidious onset with initial symptoms depending on the affected cell line.
Anemia: Weakness, lassitude, fatigability, pallor, dyspnea.
Neutropenia: Frequent infections, potentially fatal infections (sore throat, oral and pharyngeal ulcers, fever, chills, sweating, skin infections, respiratory infections, pneumonia, septicemia).
Thrombocytopenia: Bleeding manifestations (petechiae, bruises, ecchymoses), including skin bleeding, epistaxis, menorrhagia, bleeding from gums and the GI tract, retinal hemorrhage, cerebral hemorrhage. Bleeding is often the initial presentation.
Physical findings: Ecchymoses, bleeding gums, epistaxis, mouth infections. Lymphadenopathy and hepatosplenomegaly are rare. Splenomegaly warrants caution in diagnosis.
Aplastic anemia can coexist with, or progress to, clonal disorders like paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute myeloid leukemia.

Fanconi's Anemia

Inherited as an autosomal recessive disorder.
Associated with skeletal, renal, and CNS abnormalities.
Presents between 5 and 10 years of age.
Progressive pancytopenia.
Predisposition to hematological malignancies (MDS) and solid tumors (squamous cell carcinomas).

Investigations for Aplastic Anemia

Diagnosis is made with pancytopenia, absence of reticulocytes, and hypocellular (aplastic) bone marrow.
Hemoglobin, PCV, and reticulocyte count are decreased.
Peripheral blood shows pancytopenia.
Bone marrow study: Marked hypocellularity with increased fat spaces. Reduced hematopoiesis with focal areas in initial stages. Prominent lymphocytes and plasma cells.
Increased bone marrow iron stores.
Elevated serum iron and transferrin saturation.
Ferrokinetic studies: Delayed clearance of radioactive iron from the blood and increased uptake by the liver.

Severe Aplastic Anemia

Diagnosed with two out of four criteria: Neutrophil count < 0.5 x 109/L, platelet count < 20 x 109/L, reticulocyte count < 40 x 109/L, and marrow cellularity less than 25%.

Hodgkin Lymphoma

Classified based on the Cotswolds modification of the Ann Arbor Classification.
Involves lymphatic structures (lymph nodes, spleen, thymus, Waldeyer's rings, appendix, Peyer's patches) but not liver or bone marrow.
Divided into stages A or B based on the presence or absence of systemic symptoms (B symptoms).

Investigations for Hodgkin Lymphoma

Peripheral blood: Often shows normocytic normochromic anemia, sometimes microcytic in advanced stages due to iron deficiency. Total leukocyte count is usually normal, but occasionally shows neutrophil leukocytosis. Eosinophilia in about 20% of patients and thrombocytosis in some patients. Lymphopenia is associated with a poor prognosis. Leukopenia and thrombocytopenia may occur in terminal stages.
Elevated serum alkaline phosphatase usually indicates bone marrow or liver involvement.
Elevated erythrocyte sedimentation rate (ESR).
Biopsy: Fine needle aspiration of involved lymph nodes aids diagnosis. Lymph node biopsy confirms the diagnosis. Liver biopsy helps diagnose hepatomegaly.
Staging: Crucial for determining prognosis and treatment choice. Involves physical examination and investigations: chest radiographs, liver function tests, renal function tests, abdominal ultrasound, bone marrow trephine and aspirate (indicated for stage III, IV, B symptoms, or HIV-positive patients), and CT scans.
Positron Emission Tomography (PET) scan: Used for staging and management of Hodgkin lymphoma.

Chemotherapy Regimens for Hodgkin Lymphoma

ABVD: Doxorubicin (adriamycin), bleomycin, vinblastine, dacarbazine.
MOPP: Mechlorethamine (mustine hydrochloride), vincristine (oncovin), procarbazine, and prednisone.
ABVD/MOPP: Alternating cycles of MOPP and ABVD.
BEACOPP escalated: Bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone in escalated doses.

Treatment Plan for Hodgkin Lymphoma

Stage IA or IIA with no bulky disease, category A: ABVD × 4 if complete remission after 2 cycles or ABVD × 2 + involved-region radiation therapy (IRRT).
Stage IB, IIB, any stage III or IV, or bulky disease, any stage, category with 4 adverse factors: ABVD until 2 cycles past complete remission (minimum 6, maximum 8); BEACOPP escalated.

Hemophilia A (Factor VIII Deficiency)

The most common hereditary X-linked recessive disease, characterized by reduced factor VIII activity.
Males are primarily affected, while females are carriers.
Incidence is 1 in 10,000 males.
30% of cases have no family history, potentially due to acquired mutations.

Hemophilia A Inheritance

X-linked recessive inheritance.
Males typically affected, females are carriers.
Females can be hemophilic if they inherit an affected X chromosome from both parents.
Rare possibility of inactivation of the X-chromosome in females with Turner's syndrome (45,XO).

Clinical Features of Hemophilia A

Severity depends on factor VIII activity levels.
Excessive bleeding, not usually evident until around 6 months of age.
Delayed onset of post-traumatic bleeding.
Bleeding can range from mild to severe.
Petechiae are not typically observed in hemophilia.

Classification of Hemophilia A

Mild: Factor VIII level 6-30% of normal. Hemorrhage secondary to trauma or surgery, rare spontaneous hemorrhage.
Moderate: Factor VIII level 1-5% of normal. Hemorrhage secondary to trauma or surgery, occasional spontaneous hemarthrosis.
Severe: Factor VIII level ≤1% of normal. Spontaneous hemorrhage from early infancy, frequent hemarthrosis, significant bleeding after minor injuries.

Hemophilia

Frequent bleeding episodes occur spontaneously or with minimal trauma.
Hemarthrosis is prominent, affecting large joints like knees, elbows, ankles, wrists, and hips.
Recurrent bleeding leads to joint deformities and muscle atrophy.
Bleeding in muscles like calves and psoas muscles can lead to nerve compression and tendon shortening.
Bleeding time is normal, while coagulation time is prolonged.
Factor VIII assay is crucial for diagnosis and assessing disease severity.
Recombinant Factor VIII concentrate is the preferred treatment administered intravenously.
DDAVP (desmopressin) is a synthetic vasopressin analog that temporarily increases Factor VIII activity for minor bleeds.
Antifibrinolytic drugs like aminocaproic acid and tranexamic acid are used to reduce bleeding.

Thrombocytopenia

Platelet count below 150,000/µL is considered thrombocytopenia.
Immune mediated causes include primary ITP (acute and chronic) and secondary causes associated with autoimmune diseases, alloimmune reactions, drugs, and infections.
Non-immune mediated causes include DIC, TTP-HUS, mechanical destruction, and microangiopathic hemolytic anemias.
Decreased platelet production can occur due to generalized bone marrow diseases like aplastic anemia and marrow infiltration, selective impairment of platelet production due to drugs and infections, ineffective megakaryopoiesis, megaloblastic anemia, and myelodysplastic syndromes.
Splenic sequestration is another cause, occurring in hypersplenism.
Dilutional thrombocytopenia can also be present.

Immune Thrombocytopenic Purpura (ITP)

ITP is an autoimmune disorder with autoantibodies attacking platelet membrane GPIIb/IIIa and GPIb/IX, leading to increased platelet destruction.
Primary ITP is more common, with acute form prevalent in children and chronic form in adults.
Secondary ITP is associated with SLE, AIDS, Hepatitis C, viral infections, and drug therapy complications.
Clinical features are non-specific, arising from thrombocytopenia itself, often with bleeding tendencies.
Splenomegaly and lymphadenopathy are uncommon in primary ITP, suggesting alternative diagnoses when present.
Hemolysis can occur, leading to Evan's syndrome.
Most cases of acute ITP resolve within 6 months.

Hodgkin's Disease

Hodgkin lymphoma is a malignant lymphoma defined by Reed-Sternberg cells and reactive non-neoplastic cells.
Derived from B-cells with a bimodal age incidence, peaking in young adults (15-35 years) and older adults (45-75 years).
Classical Hodgkin lymphoma accounts for over 95%, with Nodular sclerosis (NS), Mixed cellularity (MC), Lymphocyte-rich (LR), and Lymphocyte depletion (LD) subtypes.
Nodular lymphocyte predominance (LP) Hodgkin's lymphoma is a less common subtype.

Chronic Myeloid Leukemia (CML)

Myeloproliferative neoplasm (MPN) characterized by excessive myeloid cell production, leading to splenomegaly and leukocytosis.
The Philadelphia chromosome (Ph) is a hallmark of CML, resulting from the t(9;22) translocation, creating a BCR-ABL1 fusion gene.
BCR-ABL1 oncoprotein causes uncontrolled kinase activity, driving cell proliferation and suppressing apoptosis.
CML progresses through three phases: chronic stable, accelerated, and blast crisis.
Diagnoses typically occur in the chronic stable phase, lasting 3-5 years without treatment.
Symptoms include fatigue, weakness, weight loss, splenomegaly, and hypermetabolic manifestations.
Signs include pallor, splenomegaly, splenic friction rub, hepatomegaly, bone pain, and sternal tenderness.
Investigations include complete blood count, peripheral blood smear analysis, and bone marrow study.
The Philadelphia chromosome is detected through cytogenetics, RT-PCR, and FISH.
Bone marrow studies show hypercellularity and fibrosis in later stages.
Peripheral blood findings show increased immature white blood cells, indicating a "left shift" and immature granulocyte presence.

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