Haematology (Quesmed) Flashcards
What is Amyloidosis?
It is a group of conditions classified by the Deposition of Extracellular Insoluble Fibrins in Organs and Blood Vessels
It can be Primary (deposition of Monoclonal Light Chains from abnormal plasma cells) or Secondary (From Multiple Myeloma or Waldenstrom’s Macroglobuminaemia)
What are the signs of Amyloidosis?
Multiple Organs affected by the Deposition of Fibrin
- Kidneys- Nephrotic Syndrome/ Renal Failure
- GI system- Macroglossia/ Malabsorption/ Hepatomegaly
- Neurological System- Neuropathies
- Vascular System- Periorbital Purpura (Raccoon Eyes)
- Joints- Asymmetrical Large Joint Inflammation
What is the diagnosis of Amyloidosis?
Tissue Biopsy (usually from the rectum)
- Apple-green birefringence when stained with Congo Red
What are the 3 causes of Anaemia of Chronic Disease?
Malignancy
Chronic Infections (TB)
Connective Tissue Diseases such as Rheumatoid Arthritis
What is seen in the bloods for Anaemia of Chronic Disease?
Initially Normochromic, Normocytic
Then becomes Microcytic, Hypochromic. Additionally LOW TIBC and HIGH FERRITIN
What is the pathophysiology of Anaemia of Chronic Disease?
IL6 is released due to the chronic disease
This stimulates Hepcidin release from the liver. this is inhibitory in Iron Absorption as it decreases the activity of Ferroportin
What is the Ann Arbor Staging System?
It is a staging system used in Hodgkin’s Lymphoma
Staging-
1) Involvement of a single nodal group
2) 2 or more nodal groups, on the SAME side of the diaphragm
3) Nodal groups on BOTH sides of the diaphragm
4) Disseminated Disease with involvement of extra-lymphatic organs (Bones or Lung)
Additional Staging Variables-
- A- if the patient Asymptomatic
- B- if there are B Symptoms
- X- if there is Bulky Nodal Disease (>10cm or >1/3of intrathoracic diameter)
- S- if Splenic involvement
- E- Extra-nodal Disease
What is Aplastic Anaemia?
It is Pancytopaenia with a Hypocellular Marrow (and no Abnormal Cells which suggest an alternative diagnosis)
Diagnosis
- Anaemia
- Thrombocytopaenia
- Neutropaenia
What are the causes of Aplastic Anaemia?
Acquired-
- Drugs (NSAIDs or Chloramphenicol)
- Infections (Hepatitis)
- Paroxysmal Nocturnal Haemoglobuinuria
Inherited-
- Fanconi’s Anaemia (Autosomal Recessive)
- Dyskeratosis Congenita (X-linked)
What are the signs of Aplastic Anaemia?
Fatigue and Pallor (Anaemia)
Infection (Leukopaenia)
Bruising and Bleeding (Thrombocytopaenia)
Identify the cause
What are the signs of Fanconi’s Anaemia and Dyskeratosis Congenita?
Fanconi’s Anaemia-
- Pigmentation Abnormalities (Palm and Nails)
- Hearing Defects
- Renal Abnormalities
- Genital Abnormalities
- Solid Tumours
- Short Stature
Dyskeratosis Congenita-
- Nail Malformations
- Oral Leukoplakia
- Reticulated Skin Rash
What does Basophilic Stippling on a Blood Film point to?
Blue Staining of Ribosomal Precipitates within the Cytoplasm of Red Blood Cells
Seen in
- Megaloblastic Anaemia
- Thalassaemias (mainly alpha)
- Sideroblastic Anaemia
- Alcohol Abuse
What does Howell Jolly bodies on a Blood Film point to?
Remnants of Red Blood Cell Nuclei
Suggests Hyposplenism
What does Schistocytes on a Blood Film point to?
Fragments of Red Blood Cells seen in Microangiopathic Haemolytic Anaemia
Could be seen in Thrombotic Thrombocytopaenia Purpura, Haemolytic Uraemia, DIC
What does Left Shift on a Blood Film point to?
Presence of Immature Cells (Unlobed nuclei) Right shift= >5 lobes
Seen in Acute Infection
Severe Left Shift= Myelocytes, Promyelocytes and Blasts= Chronic Disease
What does Leukoerythroblastosis on a Blood Film point to?
Immature Red Blood Cells and Left Shift (Immature White Cells)
It suggests Marrow Fibrosis or Invasion (Myelofibrosis, Metastatic Cancer, TB, Gaucher’s Disease)
What does Anistocytosis on a Blood Film point to?
Variation in Red Blood Cell Size
Most Common Cause of this is Iron Deficiency, especially if Low MCV
It can also be due to Sickle Cell Anaemia, and Thalassaemia and Anaemia of Chronic Disease
If High MCV, Megaloblastic Anaemia, Haemolysis with Reticulocytosis, Myelodysplasia and Liver disease
What does Acanthocytosis on a Blood Film point to?
Spiked Red Blood Cells
Altered Lipid or Protein Composition of the Red Blood Cell’s Plasma Membrane
Main Causes= Liver disease, Neuroacanthocytosis, Anorexia, Hypothyroidism and Myelodysplasia
What does Cabot Rings on a Blood Film point to?
Round Red Blood Cells of Unknown Origin
Slender Loops in the Cytoplasm
- Megaloblastic Anaemia, Severe Anaemia, Leukaemia, Lead Poisoning
What does Burr Cells on a Blood Film point to?
REGULAR Spikes
Causes- Liver Disease, Vitamin E Deficiency, End-stage renal disease, Haemolytic Enzyme Disorder Pyruvate Kinase Deficiency
What does Reticulocytosis on a Blood Film point to?
Immature Red blood cells
Haemolysis and Acute Bleeding
What does Target Cells on a Blood Film point to?
Obstructive Liver Disease
Haemoglonipathies (Thalassaemia and Sickle Cell Disease)
Post Splenectomy
What does Rouleaux Formation on a Blood Film point to?
Stacks of Aggregated Red Blood Cells
Multiple Myeloma
Waldenstrom’s Macroglobuniaemia
Inflammatory Disorders
Malignancies
When do Newborns get their blood type?
At 16 weeks after birth. So no need to cross-match until then
What are Primary Paraproteinaemias?
They are caused by the build up of Monoclonal Antibodies/ Antibody parts in the Serum or in the Urine
There may also be monoclonal plasma cells present in the marrow, soft tissue (plasmacytomas), or in the circulation
What are the 3 types of Malignant Paraproteinaemias? And what is an example of a Pre-Malignant Type?
Multiple Myeloma
Waldenstrom Macroglobuminaemia
Solitary Plasmacytoma
And Monoclonal Gammopathy of Unknown Significance is a Premalignant type
What are the features of Monoclonal Gammopathy of Unknown Significance?
Patients are asymptomatic but are POSITIVE for Monoclonal Protein on Electrophoresis
Unlike Myeloma, the Monoclonal Protein level is <30g/L and Marrow Biopsy reveals <10% of Monoclonal Plasma Cells
There will also be no evidence of End-Organ Damage
What is Multiple Myeloma?
It is a Plasma Cell Dyscrasia (Dyscrasia just means Blood Disease)
It is characterised by the abnormal proliferation of PLASMA CELLS (post-germinal B cells)
These cells secrete Monoclonal Antibodies (commonly Ig types) and Antibody fragments into the Serum and the Urine. It has many presentations but typically involves Anaemia, Infections, Hypercalcaemia and Renal Failure
What is Waldenstrom Macroglobuminaemia?
What are the signs of Hyperviscosity Syndrome?
It is a Low-grade Lymphoma where Monoclonal Plasmacytoid Lymphocytes in the marrow and organs secrete Monoclonal IgM
This IgM Deposition leads to:
- Hyperviscosity, Polyneuropathy
- Organ Infiltration (Hepatomegaly and Lymphadenopathy)
- Pancytopaenia
Hyperviscosity Syndrome= Headache, Blurred Vision, Papilloedema, Hypertension, Anaemia, Thrombocytopaenia
What is Solitary Plasmacytoma?
It presents as a Tender Swelling affecting Bone or Soft Tissue. Biopsy reveals Abnormal Collections of Plasma Cells
What are Secondary Paraproteinaemias?
They are caused by other conditions (Lymphoma (Non Hodgkin’s)) or Leukaemia (especially CLL)
How is the Platelet Plug formed?
1) Damage to the Blood Vessel causes exposure of Collagen. Von Willebrand Factor binds to Collagen which acts as a molecular anchor for platelets to join
2) Platelets adhere to the Endothelium via vWF (it basically acts as the glue). When Platelets adhere they activate and degranulate- their shape changes and they release chemicals which keeps the vessel constricted to draw more chemicals into the damaged area. This Positive Feedback Loop continues
3) The Aggregation of Platelets results in the formation of a plug which temporarily seals the break in the vessel wall
4) After the plug is formed, Coagulation is activated to form a Fibrin Mesh through the Intrinsic and Extrinsic Pathways which stabilises the Platelet Plug
What is the Intrinsic Pathway?
It is initiated when blood comes into contact with Collagen on an Injured Vessel Wall
What is the Extrinsic Pathway?
It is initiated when blood comes into contact with the Products of Damaged Tissue
What happens at the end of the Coagulation Cascade?
Intrinsic and Extrinsic Pathways both lead to the production of Factor Xa
This converts Prothrombin to Thrombin
Thrombin converts Fibrinogen to Fibrin
Thrombin also converts Factor XIII to XIIIa
Factor XIIIa converts Fibrin to a Stable Fibrin Clot
Which Clotting Factors are inhibited by Warfarin?
2, 7, 9, 10 (All produced through Vitamin K)
What are the 5 Acute Complications of Blood Transfusion, how do they Present and how are they Managed?
1) Allergy-
- Presents as Urticaria or Angioedema or Anaphylaxis
- Management- stop Transfusion and give Saline, Adrenaline (if Anaphylactic), Chlorphenamine and then Hydrocortisone
2) Acute Haemolytic Transfusion Reaction-
- Caused by giving Incompatible Blood
- Presents as Fever, Hypotension and Anxiety
- Management- Stop the transfusion, Give Saline and Treat DIC
3) Febrile Non Haemolytic Transfusion Reaction-
- Fever, Rigor/ Chills but otherwise they are well
- Management- SLOW the transfusion and give them Paracetamol
4) Transfusion-related Lung Disease-
- Pulmonary Oedema and Acute Respiratory Distress Syndrome
- Management- Stop Transfusion, Give Saline, Treat ARDS
5) Transfusion-associated Circulatory Overload
- Presents with Fluid Overload
- Management- Slow/ Stop the transfusion and give them Furosemide
What are the 2 Late Complications of Blood Transfusion?
1) Delayed Haemolytic Transfusion Reaction
- An Exaggerated Response to a Foreign Antigen that the patient has been exposed to before.
- Patients present with Jaundice, Anaemia and Fever usually 5 days AFTER transfusion
2) Transfusion-Associated Graft-Versus-Host Disease
- Donor Blood Lymphocytes attack the Recipient’s Body
What is Essential Thrombocytosis?
It is a Myeloproliferative Disorder caused by Dysregulated Megakaryocyte (PLATELET PRECURSOR) Proliferation
It is most common in female patients in 50-70 years old
What are the signs and symptoms of Essential Thrombocytosis?
HALF of patients are asymptomatic btw
Platelet count (>450 x10^9/L)
JAK2 V617F mutation is present in 50-60% and it is HIGH in ESSENTIAL Thrombocytosis and not present in Secondary Thrombocytosis
- Thrombosis
- Bleeding (Gastrointestinal or Intracranial)
- Headache and Dizziness (secondary to Hyperviscosity)
- Splenomegaly
- Erythromelalgia (Red/Blue Discoloration of the Extremities, often accompanied by a Burning Pain)
- Livedo Reticularis (Net-like Purple Rash)
What are the key differentials for Essential Thrombocytosis?
Secondary (Reactive) Thrombocytosis (if triggered by Infection or Trauma)
- Bleeding and Thrombotic Complications are uncommon in Secondary Thrombocytosis
What is the management of Essential Thrombocytosis?
Hydroxycarbamide (reduces Platelet count)
If Severe/ High Risk Patients= Hydroxyurea (suppresses bone production of platelets)
What are the causes of Pancytopaenia?
1) Causes of decreased marrow haematopoetic function
- Chemotherapy and Radiotherapy
- B12 and Folate Deficiency
- Marrow Infiltration due to Haematological Malignancies
- Myelofibrosis
- Multiple Myeloma
- Parvovirus Infection in Haemolytic Disease (like Sickle Cell Anaemia)
2) Inherited causes of marrow failure
- Fanconi’s Anaemia (autosomal recessive) and Dyskeratosis Congenita (X-linked condition)
3) Increased Destruction of Blood Cells peripherally
- This is seen in Conditions affecting the Liver (Hepatitis B/C, Autoimmune Hepatitis, Cirrhosis)
4) Immune Destruction of Blood Cells
- Drugs- Sulphonamide or Rifampicin
What are the caused of Neutrophilia? (High Neutrophils)
Severe Stress
- Trauma, Burns, Surgery, Haemorrhage, Seizures
Active Inflammation
- Polyarteritis Nodosa
- Myocardial Infarction
- Disseminated Malignancy
Corticosteroid use (less common)
Myeloproliferative Disease (Like CML)
What are the causes of Neutropenia? (Low WBC)
Sepsis, Viral infections, Drugs (Carbimazole), Marrow Failure
Hypersplenism, Felty’s Syndrome, SLE
What are the causes of Agranulocytosis? (Low Eosinophils and Basophils)
Drug Causes (the 3 C’s)
Clozapine
Carbamazepine
Carbimazole
What are the causes of Lymphocytosis?
Acute Viral Infections
Chronic Atypical Infections (like TB, Brucella, Toxoplasmosis)
Blood Cancers (Leukaemia, Lymphoma)
What are the causes of Eosinophilia?
Infections (parasitic worms)
Allergy (including drug allergy)
Inflammatory Diseases (like Eosinophilic Granulomatosis and Polyangiitis)
What are the causes of Thrombocytopaenia?
Decreased Production (Marrow Disease or Myelosuppressive Drugs (HEPARIN))
Increased Destruction (Immune-regulated, Hypersplenism, Consumption)
It may also be FUNCTIONAL Thrombocytopaenia (where platelet count is normal but platelet bleeding pattern occurs)- like Von Willebrand Disease and Inherited Platelet Abnormalities
What disease can progress to Acute Myeloid Leukaemia and what is seen in Bone Marrow Biopsy?
Myelodysplasia
Ring Sideroblasts are seen on Biopsy
What are the signs of Tapeworm and how is it managed?
Lots of Meat Consumption (Especially Raw Meat)
Large “Grapefruit Seeds” in Stool
Management- Prazquantel and Niclosamide
What’s the first thing that should be done if a patient presents with Thrombocytopaenia?
Examine them for signs of Bleeding
What are the signs of Immune Thrombocytopaenia?
Purpuric Rashes and Often preceded by Viral Infection
What is Haemolytic Anaemia?
Destruction of Red Blood Cells
What are the biochemical signs of Haemolytic Anaemia?
Low Haemoglobin
High Unconjugated Bilirubin
May be Reticulocytosis
Raised LDH
Raised Urinary Urobilinogen
What is the pathophysiology of Haemolytic Anaemia?
Intravascular Haemolysis results in the release of Cellular Contents (like Haemoglobin) into the circulation
This excess of Haemoglobin is dealt with in many ways- it combines with Haptoglobin, Albumin (Metheamalbuminaemia), loss in the Urine (Haemoglobinuria) and stored in Tubular Epithelial Cells as Haemosiderin and shed into urine (Hemosiderinuria)
What are the 4 causes of Intravascular Haemolytic Anaemia?
- Intrinsic Cell Injury (G6PD)
- Intravascular Complement Mediated Lysis (some Autoimmune Haemolytic Syndromes)
- Mechanical Injury (valves)
- Acute Transfusion Reactions
What are the signs of Haemolytic Anaemia?
Signs of Anaemia
Jaundice
Splenomegaly (if Extravascular)
Schistocytes on Blood Film (Broken Red Blood Cells)
High Unconjugated Bilirubin
Low Haptoglobin (as they are being used to ship out broken Haemoglobin)
Dark Urine (Haemoglobuminuria)
Patients may have PROSTHETIC VALVES which cause Intravascular Haemolysis
What is G6P Deficiency?
It is an X-linked Recessive Red Cell Enzyme Disorder which presents in the Neonatal Period with Jaundice or later in life with Episodic Intravascular Haemolysis following Exposure to Oxidative Stressors
What can trigger G6PD?
Illness or Infection
Fava Beans
Henna
Some Drugs (Nitrofurantoin, NSAIDs, Aspirin, Dapsone, Primaquine)
What are the investigations and management of G6PD?
Blood Film- Heinz Bodies and Bite Cells
Diagnostic test- G6PD Enzyme Assay
Management- Avoid Precipitants (patients may need Transfusion)
What is Extravascular Haemolytic Anaemia?
It occurs in the Liver and the Spleen
It is caused by
- Abnormal Red Blood Cells (Sickle Cell Anaemia and Hereditary Spherocytosis)
- Normal Cells being marked by Antibodies for Splenic Phagocytosis
What is Hereditary Spherocytosis?
It is an Autosomal Dominant condition
The Spleen removes Abnormal Sections of RBC Membranes resulting in a low SA:V ratio and cells become Spherocytes and are Haemolysed for this (Extravascular Haemolysis)
What are the signs and management of Hereditary Spherocytosis?
Neonatal or Childhood onset
- Jaundice, Anaemia and Splenomegaly
Management- Folic Acid but Splenectomy before they turn 5 years old is curative
What is the test for Autoimmune Haemolytic Anaemia?
Direct Coomb’s Test
What are the 2 types of Autoimmune Haemolytic Anaemia?
Warm and Cold
What are the causes of Warm Autoimmune Haemolytic Anaemia?
It is an IgG mediated Extravascular Disease where the Spleen tags cells for Splenic Phagocytosis
Causes-
- Idiopathic
- Lymphoproliferative Neoplasms (CLL and Lymphoma)
- Drugs such as Methyldopa
- SLE
What are the causes of Cold Autoimmune Haemolytic Anaemia?
It is an IgM-mediated Haemolytic Disease where IgM fixes Complement causing Direct Intravascular Haemolysis
Causes-
- Idiopathic
- Post-infection (2-3 weeks after infection (like EBV usually and Mycoplasma))
What are 5 examples of Coomb’s Negative Haemolytic Anaemia?
1) Microangiopathic Haemolytic Anaemia
2) Paroxysmal Nocturnal Haemoglobinuria
3) Physical Lysis of Red Cells (like in Malaria/ Prosthetic Valves)
4) Haemolytic Uraemic Syndrome (due to E. Coli)
5) Infectious causes of DIC- Meningococcaemia
Which Clotting Factors are affected (reduced) in Haemophilia A and B?
Haemophilia A- Factor 8
Haemophilia B- Factor 9
What are the signs of Haemophilia A and B and how are they managed?
Early in Life with Deep and Severe Bleeding into Soft Tissues, Joints and Muscles (Haemoarthrosis and Muscular Haematomas)
PROLONGED APTT
Haemophilia A- managed with Desmopressin and Recombinant factor 8 if severe
Haemophilia B- Recombinant factor 9
Which type of Haemophilia is more common?
Haemophilia A
What are the 7 causes of a high INR?
- Overdose of Anticoagulation
- Drug Interactions (antibiotics, antifungals, aspirin, amiodarone)
- Herbal Products
- Increased alcohol consumption
- Decrease in consumption of Vitamin
- Liver Failure
- Infection
What is needed in the assessment of a high INR?
History
- Find out about Anticoagulation
- Concurrent Illness
- Change in Medication
- Change in Diet/ Lifestyle
- History of Falls/ Injuries
- History of Blood Loss
Blood
- FBC- look for Anaemia and Infections
- Clotting screen
Examination
- Evidence of bleeding
What is the management of a high INR?
Major Bleeding-
- Stop Anticoagulants
- Administer IV Vitamin K
- Administer Fresh Frozen Plasma or Prothrombin Complex
Minor Bleeding-
- Stop Anticoagulants
- Administer IV vitamin K
- Repeat INR after 24 hours- they may need more Vitamin K
No bleeding with INR>8-
- Stop Anticoagulants
- Administer IV or Oral Vitamin K
- Repeat INR after 2 hours
No Bleeding with INR> 5-
- Withhold 1-2 doses of anticoagulant
- Review the maintenance dose of anticoagulant
What tests does the Clotting Panel measure?
Prothrombin Time (PT)- (INR is derived from PT btw)- measures Extrinsic Clotting pathway
APTT- measures Intrinsic Clotting pathway
What do Blood Tess for Von Willebrand’s disease reveal?
Normal PT
Normal TT
Prolonged APTT
Prolonged Bleeding
Normal Platelet Count
What are the 4 common products of Transfusion?
Red Blood Cells-
- Transfused Red Cells last around 50-60 days
- (normally 120 days in the normal body)
Fresh Frozen Plasma-
- It is used in patients with Coagulopathy (impaired coagulation) by replacing clotting factors
Platelets-
- Lifespan of 10 days before they are phagocytosed in the Spleen and Liver
Cryoprecipitate-
- When Fresh Frozen Plasma is thawed overnight. It contains Fibrinogen, Factor 8 and Von Willebrand Factor. It is used when patients have MASSIVE bleeding and Low Fibrinogen
What is Macrocytic Anaemia and what are the 2 types?
When RBCs are larger than normal
Consists of Megaloblastic and Non-Megaloblastic Anaemia
What are the causes of Non-Megaloblastic Macrocytic Anaemia?
Hypothyroidism (Hashimoto’s Thyroiditis)
Alcoholism
Reticulocytosis
Also Chronic Liver Disease- due to Blood Loss (Varices), Hyposplenism, Alcoholism and Nutritional Deficiencies
What are the causes of Megaloblastic Macrocytic Anaemia?
The Failure to synthesise adequate amounts of DNA
Due to deficiency in B12 (look for NEUROLOGICAL SIGNS) or Folic Acid
Low B12 levels can be due to Pernicious Anaemia, Dietary Insufficiency and Malabsorption
What investigations should be ordered in Megaloblastic Anaemia?
Macrocytic Red Cells with Megaloblastic Features (Enlarged Abnormal Nuclei, Basophilic Cytoplasm)
Low Serum B12 (in Pernicious Anaemia)
Parietal Cell or Intrinsic Factor Autoantibodies
What is the cause of Pernicious Anaemia?
Autoantibodies against Intrinsic Factor
What are the 3 causes of Microcytic Anaemia?
Iron Deficiency Anaemia
Sideroblastic Anaemia
Alpha and Beta Thalassaemia
What is Myelofibrosis and what are the signs?
It is a Myeloproliferative Disorder of unknown cause- characterised by Marrow Fibrosis
It can present as Pancytopaenia
It is more common in Elderly Patients
Signs
- Weight Loss, Fever, Night Sweats, Fatigue
- Splenomegaly, Abdominal Discomfort
- Marrow Failure- Anaemia, Recurrent Infections, Bleeding
- Hepatomegaly (seen in 50% of patients)
What is the Diagnosis and Management of Myelofibrosis?
Blood Film- Poikilocytes (Tear shaped Red Blood Cells)-
It can be difficult to aspirate the Bone resulting in a DRY TAP
Diagnosis- Bone Marrow Biopsy
Management- Stem Cell Transplantation or Immunomodulatory Drugs like Thalidomide
What is the first investigation in Pancytopaenia?
Blood Film
What is Multiple Myeloma?
It consists of the Abnormal Clonal Proliferation of post-germinal B Cells (Plasma Cells)
They will secrete lots of Antibodies and Antibody Fragments into the Serum and the Urine
There is also a deficiency of Functional Antibodies leading to Hypogammoglobuminaemia
What are the signs of Multiple Myeloma?
CRABHAI
Hypercalcaemia- Due to Osteoclast-mediated Bone Resorption
Renal Impairment- due to light-chain deposition in the Kidneys and Hypercalcaemia
Anaemia- Marrow infiltration can lead to other Cytopaenias as well (Leukopaenia and Thrombocytopaenia)
Bone Pathology- Fractures and Bone Pain
Hyperviscosity- Headache, Visual Disturbances and Thrombosis
Amyloidosis
Infection- Due to Leukopaenia
What investigations should be ordered in Multiple Myeloma?
Bloods. FBC- Anaemia, U&Es- Renal Impairment (high Creatinine), Hypercalcaemia
Blood Film- Rouleux Formation
Xray and CT/MRI- Osteolytic Bone Lesions and Pathological Fractures
Diagnostic-
- Serum or Urine Electrophoresis= Paraprotein Spike (IgG)
- Serum free light chain assay- Bence Jones Protein
- Tissue diagnosis by Bone Marrow Aspirate and Biopsy- if >10% plasma cells in bone marrow
What is the management of Multiple Myeloma?
Haematopoetic Stem Cell Transplant
- Induction therapy needed (Thalidomide, Dexamethasone, Bortezomib) or Chemotherapy
Unsuitable for Transplant- MPT therapy
- Melphalan, Prednisolone and Thalidomide. Give Lenalidomide instead of Thalidomide if needed
Complication management-
- Analgesia, Bisphosphonates, Surgical Stabilisation for Bone Disease
- Influenza and Pneumococcal Vaccination for Infection Prevention
- Erythropoeitin (+/- Transfusion) for Anaemia
What is Non-Hodgkin’s Lymphoma commonly associated with?
Viral Infection and Immunodeficiency
- Helicobacter Pylori= Gastric MALT (Mucosa-associated Lymphoma Tissue) (lymphoid infiltrates seen)- Give PPI and 2 antibiotics
- EBV= Burkitt’s Lymphoma and AIDS related CNS Lymphoma
- Hep C= Diffuse Large B-cell Lymphoma and Splenic Marginal Zone Lymphoma
- Human T cell Lymphotrophic Virus Type 1= T Cell Lymphoma
What are the signs and diagnosis findings of Non-Hodgkin’s Lymphoma?
Non Tender, Firm, Painless Lymphadenopathy (SYMMETRICAL, unlike Hodgkin’s)
Splenomegaly/ Hepatomegaly
B symptoms are more common in Non-Hodgkin’s (Weight Loss, Fever, Night Sweats)
Diagnosis-
- Elevated LDH which is a POOR PROGNOSTIC MARKER
- Blood Film- Nucleated Red Cells and LEFT SHIFT (presence of white cell precursors)
- Circulating Lymphoma cells in Blood Film (Basophilic Vacuolated)
What are some signs of Burkitt’s Lymphoma?
African Origin Child
Jaw Lymphadenopathy
What is Paroxysmal Nocturnal Haemoglobinuria and how does it present?
It is a rare acquired Stem cell Disorder of Unknown Aetiology
An Abnormal Surface Glycoprotein is expressed on a subclone of Red Blood Cells. This MARKS THESE CELLS for Complement-mediated Haemolysis
Presentation-
- Early Adulthood. Intravascular Haemolysis at Night OR Morning and it may be associated with other Stem Cell Defects as well as an Increased Risk of Thrombosis and Erectile Dysfunction
ANAEMIA/ LOW WCC/ THROMBOCYTOPAENIA
How is Paroxysmal Nocturnal Haemaglobinuria Diagnosed and Managed?
Diagnosed with Flow Cytometry
Management- Eculizumab (this inhibits formation of the Membrane Attack Complex of the Complement Cascade
It improves the quality of life but doesn’t improve mortality
What is Pernicious Anaemia?
It is a Deficiency of Red Blood Cells caused by the lack of B12 in the blood
This is due to a deficiency of INTRINSIC FACTOR
What are the causes of B12 Deficiency?
Gastric Causes- Pernicious Anaemia, Chronic Severe Atrophic Gastritis
Pancreatic- Any cause of Pancreatic Insufficiency (Like Cystic Fibrosis)
Small Bowel Bacterial Growth- as Bacteria utilize B12, Terminal Ileal Resection, Severe Terminal Ileal Disease (Crohn’s)
Tuberculosis
Metformin (so suspect in Diabetics)
Zollinger-Ellison Syndrome
What are the blood test results in Pernicious Anaemia?
Low Hb
Low B12
Low or Normal Folate
Low Reticulocyte
High MCV
High MCH
Abnormally Large and Oval-shaped RBCs in Blood Smear
Hypersegmented Neutrophils on Blood Film
Normal MCHC
Antibodies against Intrinsic Factor (More Specific) and/or Parietal Cell may be present in Pernicious Anaemia (Parietal Cell Antibodies are more Sensitive though)
What is the management of Pernicious Anaemia?
Life-long Replacement therapy with Cobalamin
Also advice them on long-term GI consequences such as Gastric Cancer and Carcinoids
What is Polycythaemia?
Increase in RBC, Haematocrit and Hb
Divided into Relative and Absolute Polycythaemia
What is Absolute and Relative Polycythaemia?
Absolute-
- Plasma Volume is Normal and the Red Cell Mass will be raised
- Divided into Primary and Secondary
Relative-
- Haemoglobin is high but all due to low Plasma Volume (remember Hb is measured as a Concentration). This can be due to DEHYDRATION or DIURETICS
What is Gaisbock’s Syndrome?
Pseudo-Polycythaemia
It is more common in Young Male Adults- particularly in smokers, it is associated with Hypertension
This reduced Plasma Volume and leads to a Raised Haemoglobin
What is Primary and Secondary Absolute Polycythaemia?
Primary- Independent of EPO (Erythropoeitin)
Secondary- Driven by Excess EPO (such as due to Chronic Hypoxia- like COPD. Or inappropriate secretion of EPO like in a paraneoplastic condition
What are the signs of Polycythaemia (Primary and Secondary)?
- Fatigue
- Headache
- Visual Disturbances (Due to Hyperviscosity)
- Pruritus (after hot bath) and Erythromelalgia (burning sensation on fingers and toes)
- Face is RED on Examination
- Arterial and Venous Thrombosis (MI, Stroke, VTE)
- Haemorrhage
- Increased risk of Gout (Hyperuricaemia occurs due to increased Cell Turnover)
- Splenomegaly
What are the signs of Polycythaemia Rubra Vera (Primary Polycythaemia)?
Hyperviscosity (Chest Pain, Myalgia, Weakness, Headache, Blurred Vision, Loss of Concentration)
“Ruddy Complexion”
Splenomegaly
Raised HAEMATOCRIT
Low EPO
HIGH WBC and PLATELETS
JAK-2 MUTATION
What is the management of Polycythaemia? (secondary to Waldenstrom’s Macroglobuminaemia)
Venesection (Phlebotomy)
What is Sickle Cell Disease?
It is a Genetic Condition where Normal Haemoglobin has the tendency to form Abnormal Haemoglobin Molecules (HbS) upon
Deoxygenation
It is Autosomal Recessive
When Deoxygenated, the HbS undergoes Polymerisation and this forms Red Blood Cells that are Sickle-Shaped
What is the mechanism of Hyposplenism in Sickle Cell Anaemia?
Sickle Cells commonly sequester in the Spleen and undergo Phagocytosis by the Reticular Endothelial System which leads to EXTRAVASCULAR HAEMOLYSIS
This leads to Splenic Congestion and Splenomegaly
The spleen is necessary for Phagocytosis and the Immune System
So due to a Compromised Spleen, there is reduced Immune Function
What is the most common Acute Presentation of Sickle Cell Disease?
Painful Vaso-Occlusive Crises- this is caused by Microvascular Obstruction due to cell sickling which is triggered by Local Hypoxia (like Cold weather causing blood to rush away from fingers)
Acute Chest Crises-
- This is the most dangerous presentation. The cause is unknown. Patients present with Tachypnoea, Wheeze, Cough, Hypoxia and Pulmonary Infilitrates
It usually presents with Progressive Anaemia as Foetal Haemoglobin Levels Fall
What Investigations are ordered in Sickle Cell Anaemia?
Bloods-
- MICROCYTIC Anaemia
- Reticulocytosis
- High Unconjugated Bilirubin
Blood Film-
- Sickle Cells
- Target Cells
- Reticulocytosis with Polychromasia
- Features of Hyposplenism (Howell Jolly Bodies, Nucleated Red Blood Cells)
Definitive Diagnosis-
- Haemoglobin Electrophoresis +/- Genetic Testing
What is the management of Sickle Cell Crisis and Chronic Sickle Cell Disease?
Sickle Cell Crisis-
- High Flow Oxygen
- IV Fluids (Morphine Sulphate)
- Analgesia
- Maybe Antibiotics (Ceftriaxone)
Chronic Sickle Cell Disease-
- Hydroxycarbamide (Hydroxyurea) if frequent crises in order to increase Fetal Haemoglobin Concetration
- Regular Exchange transfusions may be needed for Severe Anaemia
- Vaccinations and Antibiotics needed as Prophylaxis (if Splenic Infarcts and Subsequent Immunocompromise)
Acute Chest Crisis-
- Oxygen
- Antibiotics
- Exchange Transfusion
What are the complications of Sickle Cell Disease?
1) Splenic Infarction and Subsequent Immunocompromise
2) Sequestration Crisis (a dangerous amount of blood becomes trapped in the Spleen- which causes a drop in Plasma Volume)
3) Osteomyelitis
4) Stroke
5) Poor Growth
6) Chronic Renal Disease
7) Retinal Disorders
8) Pulmonary Fibrosis and Pulmonary Hypertension
9) Iron OVERLOAD- due to repeated Transfusion
10) Red Cell Aplasia (due to Parvovirus B19 infection in patients with Chronic Haemolytic Anaemia)
What features make an Acute chest Crisis unlikely in Sickle Cell Anaemia?
Clear Chest
Reticulocytosis and Hyperbilirubinaemia
Lack of Fever
What is the Reticulocyte Count in Aplastic Crisis in Sickle Cell Anaemia?
Low Reticulocyte count- as Bone Marrow is suppressed
What is the Reticulocyte Count in Haemolytic Crisis in Sickle Cell Anaemia?
High Reticulocyte count
What is the most important side effect of Corticosteroids?
Adrenal Suppression
- Due to exogenous steroids being taken, the adrenal glands stop producing endogenous steroids
- When exogenous steroids are stopped, it leads to Adrenal Insufficiency
- This can lead to SHOCK- Hyperkalaemic Hypotension. Management= IV Hydrocortisone
How can Adrenal Suppression be prevented in Corticosteroid intake?
1) If taken for <3 weeks then the steroids can safely be stopped abruptly
2) If taken for longer than this, they must slowly be tapered down
3) “Sick Day Rules”- if acutely unwell, double the usual dose of Prednisolone or supplement IV Hydrocortisone if they can’t take oral medication
4) If Nil-By-Mouth (including vomiting)- convert the increased daily dose of Prednisolone to the equivalent IV Hydrocortisone
How can Adrenal Suppression be prevented in Corticosteroid intake?
1) If taken for <3 weeks then the steroids can safely be stopped abruptly
2) If taken for longer than this, they must slowly be tapered down
3) “Sick Day Rules”- if acutely unwell, double the usual dose of Prednisolone or supplement IV Hydrocortisone if they can’t take oral medication
4) If Nil-By-Mouth (including vomiting)- convert the increased daily dose of Prednisolone to the equivalent IV Hydrocortisone
What should be done due to the risk of Immunosuppression by Corticosteroids?
Risk of Reactivation of Latent Infections
- Have a low threshold for detecting TB
- If they have Cold Sores or Shingles, start Acyclovir ASAP
Raised Risk for New Infections
- Have a low threshold for cultures
Avoid LIVE VACCINATIONS
What are the additional side effects of Corticosteroids?
Dermatological
- Cushingoid Appearance
- Acne
- Thinned skin with steroids
Endocrine
- Hyperglycaemia
- Cushing’s Disease (HYPOKALAEMIC HYPERTENSION)
- Growth Retardation
MSK
- Muscle Wasting
Psychiatric
- Mood Swings
- Worsening of Psychiatric Conditions
GI
- Dyspepsia
Ophthalmic
- Glaucoma
- Cataracts
What is a side effect of Mineralocorticoids?
Fluid Retention
What is Sideroblastic Anaemia?
It is a Microcytic Anaemia that is commonly mistaken for Iron Deficiency Anaemia
It occurs due to Ineffective Erythropoeisis (red cell production). This results in Increased Iron Absorption and deposition within the bone marrow and in other areas
This manifests as Sideroblastic Inclusions within the RBC cytoplasm (seen on blood film) and as Haemosiderosis of the Liver, Heart and Endocrine Organs (similar to Hereditary Haemochromatosis)
What are the signs of Sideroblastic Anaemia?
Microcytic Anaemia that is refractory to Iron Therapy
There will be a very high level of Ferritin and Iron
Ring Sideroblasts in the Marrow
Pappenheimer Bodies are positive (staining for Iron)
What are the causes of Sideroblastic Anaemia?
Congenital Causes (X linked, Recessive or Dominant)
Acquired Causes- Drug/ toxin related (Alcohol, Lead Poisoning, Isoniazid use)
What are the signs of Lead Poisoning?
1) Abdominal Pain
2) Bowel Disturbance
3) Motor Peripheral Neuropathy
4) Paraesthesia
5) Confusion
6) Metallic Taste in Mouth
7) Haemolysis (Dark Urine and Pallor)
8) DENSE Metaphysial lining on Radiograph
Blue line on gum
What are the indications for Splenectomy?
- Trauma and Rupture (EBV Infection)
- Haemolytic Anaemia and Idiopathic Thrombocytopaenia Purpura
What 4 vaccinations do patients need Post-Splenectomy?
Pneumococcal Vaccination (regular boosters every 5 years)
Seasonal Influenza Vaccination (every autumn)
Haemophilus Influenza B (One Off)
Meningitis C (One Off)
- they will also need life-long Low-dose Prophylactic Antibiotics (-cillins or Erythromycin if they are allergic)
What is the Target INRs for different diseases?
AF= 2-3
Aortic Valves= 2-3
Mitral Valves= 2.5-3.5
VTE= 2-3
VTE while on Warfarin= 3-4
What is Thalassaemia?
It is an AUTOSOMAL RECESSIVE Genetic Condition that leads to Abnormal Haemoglobin production
What is the pathophysiology of Alpha Thalassaemia?
There are non-functioning copies of the four Alpha Globin Genes
What are the signs of Alpha Thalassaemia?
Jaundice
Fatigue
Facial Bone Deformities
How is Alpha Thalassaemia Diagnosed and Managed?
Genetic Testing, an FBC would reveal Microcytic Anaemia
Management-
- Blood Transfusions and Stem Cell Transplantation
What is the pathophysiology of Beta Thalassaemia?
Non Functioning copies of 2 Beta Globin Genes
Thalassaemia Trait (Minor)
Beta Thalassassaemia Major (null mutations in both copies)
What are the signs of Beta Thalassaemia Major and Minor?
Minor-
- Microcytosis and Mild Anaemia
- But patients are usually Asymptomativ
Major-
- Severe Symptomatic Anaemia at 3-9 months of age where levels of Foetal Haemoglobin fall (which does not contain the beta haemoglobin)
- Frontal Bossing (Prominent Foreheads)
- Maxillary Overgrowth (Upper Jaw Grows)
- Extramedullary Hematopoeisis (Hepatosplenomegaly)
What is the management of Beta Thalassaemia?
Regular Blood Transfusions
Give them Iron Chelating Agents to decrease the risk of Iron Overload- like Desferrioxamine
What happens if a patient has 4 dysfunctional alpha globin genes?
Hydrops Foetalis- Death in Utero
What are the signs of Transfusion-related Iron Overload?
Joint Symptoms (MCP Joints especially)
Hyper-pigmentation
Signs of Pituitary and Heart Failure (Leg Swelling and Shortness of Breath)
What investigations should be ordered to confirm Thalassaemia?
Haemoglobin electrophoresis- Increased HbF or HbA2
Which Ethnicity is more correlated to Thalassaemia?
Mediterranean
What is Thrombophilia?
It is a condition where there is an increased risk of Venous Thrombosis due to issues with Coagulation
What are the signs for the 3 types of Thrombophilia?
Consider this if Recurrent VTEs across Family (so seems like it is inherited)
Factor V Leiden
- Most common inherited Thrombophilia
- Caused by mutation in Clotting Factor 5
- It ends up being Resistant to inactivation by Protein C so it continues clotting
- As they are resistant to Protein C, WARFARIN has no use
Protein C Deficiency
- It inhibits Factor 5 and 8
- This is higher in Southeast Asian Patients
Antithrombin 3 Deficiency
- It inhibits Factor 2a, 9a, 10a and 11a
- Homozygosity causes Death In Utero
Which DVT risk factor presents a HIGH RISK?
Recent Surgery- as all 3 parts of Virchow’s Triad are affected
What is Thrombotic Thrombocytopaenia Purpura?
It is caused by the Abnormally Cleaved von-Willebrand Factor which leads to Platelet Aggregation, Thrombus Formation and Systemic Microangiopathy
This occurs due to Abnormal ADAMST113 Activity
What are the 2 causes of Thrombotic Thrombocytopaenia Purpura?
Hereditary- Congenital mutation of ADAMST13
Autoimmune Inhibition of ADAMST13
What are the 5 Signs of Thrombotic Thrombocytopaenia Purpura?
- Fever
- Thrombocytopaenia Purpura
- Microangiopathy Haemolytic Anaemia
- CNS Involvement- Headache, Confusion, Seizures
- AKI
What investigations should be ordered in Thrombotic Thrombocytopaenia Purpura?
Diagnostic= Low ADAMST13 activity
- Urine dipstick- Haematuria and Non-nephrotic range Proteinuria
- FBC- Normocytic Anaemia, Thrombocytopaenia and MAYBE raised Neutrophil
- U&Es- Raised Creatinine and Urea (cos there is AKI)
- LFT/ LDH and D-dimer will be raised
- Blood Film= Reticulocytes and Schistocytes
- Haptoglobulins will be low (as expected in Haemolysis)
- Clotting is normal
What investigations should be ordered in Thrombotic Thrombocytopaenia Purpura?
Diagnostic= Low ADAMST13 activity
- Urine dipstick- Haematuria and Non-nephrotic range Proteinuria
- FBC- Normocytic Anaemia, Thrombocytopaenia and MAYBE raised Neutrophil
- U&Es- Raised Creatinine and Urea (cos there is AKI)
- LFT/ LDH and D-dimer will be raised
- Blood Film= Reticulocytes and Schistocytes
- Haptoglobulins will be low (as expected in Haemolysis)
- Clotting is normal
What is the management of Thrombotic Thrombocytopaenic Purpura?
Plasma Exchange within 24 hours
Caplacizumab may be indicated
What conditions present with a low ESR?
Polycythaemia
Sickle Cell Disease
Severe Leukocytosis
Corticosteroid Use
Hereditary Spherocytosis
OTHER Anaemias don’t have low ESR
What is Tumour Lysis Syndrome? What are the signs?
It is due to the rapid death of Tumour cells through Chemotherapy
After Leukaemia/ Lymphoma Treatment
Signs-
- Dysuria/ Oliguria
- Abdominal Pain
- Weakness
- Confusion and Muscle Cramps
What investigations should be ordered in tumour Lysis Syndrome?
What is the management?
Raised Potassium and Phosphate
Low Calcium
Raised Uric Acid
ECG may show Hyperkalaemia
Management-
- Correct Electrolytes and give fluid
- Rasburicase for the Uric Acid
What is Von Willebrand Disease?
It is the most common Inherited Bleeding Disorder
Usually in FEMALEs (Haemophilia is usually in MALES)
It is Autosomal Dominant
It is caused by reduced quantity or function of Von Willebrand Factor- which normally linked platelets to the endothelium and stabilised Factor 8
What are the signs of Von Willebrand Disease?
Prolonged bleeding from Wounds and Surgical Incisions
Easy Bruising
Menorrhagia
Epistaxis
GI Bleeding
(unlike Haemophilia A and B, bleeding into Joints is RARE)
(Mucosal Bleeding is also RARE in Haemophilia)
What are the blood results in Von Willebrand Disease?
Normal PT
Prolonged APTT
Prolonged Bleeding time
What is the first line management of Von Willebrand Disease?
Desmopressin
What must girls with Haemophilia always have?
Either an affected father and carrier/affected mother
Or
They must have Turner’s Syndrome
What are the 5 causes of Massive Splenomegaly?
Myelofibrosis
CML
Visceral Leishmaniasis
Malaria
Gaucher’s Syndrome
What increases the risk of Anaphylaxis Reactions to Transfusion?
IgA Deficiency
What is the management of Neutropaenic Sepsis? (If Temp>38C while on cancer treatment)
IV Piperacillin and Tazocin
What are the triad of symptoms for Wernicke’s Encephalopathy?
Confusion
Ataxia
Ophthalmoplegia/ Nystagmus
(Not all 3 signs are needed)
What is the treatment for Wernicke’s Encephalopathy?
Thiamine (B1) so give it to any patient with Chronic Alcohol Abuse
