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
