Haematology Flashcards

Question

What are the pathological consequences of anaemia?

Answer 1

``` Myocardial fatty change Aggravate angina/claudication Fatty change in liver Skin and nail atrophic changes CNS cell death (cortex and basal ganglia) ```

Answer 2

Red cell life span is approx 120 days. Production in the bone marrow. Removal in the spleen, liver, bone marrow and through blood loss. Reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), reticulocytes develop and mature in the bone marrow and then circulate for about a day in the bloodstream before developing into mature red blood cells.

Answer 3

Microcytic Normocytic Macrocytic

Answer 4

``` Iron deficiency Chronic disease Thalassaemia - haemoglobinopathy Rarely Congenital sideroblastic anaemia Lead poisoning ```

Answer 5

Acute blood loss Anaemia of chronic disease Combined haematinic deficiency - two factors (iron deficiency and B12 deficiency)

Answer 6

``` B12/folate deficiency Alcohol excess/liver disease Hypothyroid disease HAEMATOLOGICAL –Antimetabolite therapy –Haemolysis –Bone marrow failure –Bone marrow infiltration ```

Answer 7

``` Tests of deficiency Ferritin Iron studies Tests of causes Treatment ```

Answer 8

IF antibodies Schilling test Coeliac antibodies B12 replacement

Answer 9

``` Thorough history and examination FBC and blood film Reticulocyte count - to check whether there is abnormal production or destruction U&Es, LFTs, TSH B12, folate, ferritin Discuss with haematologist ```

Answer 10

Disorders of quality (abnormal molecule or variant haemoglobins) e.g. Sickle cell disease Disorders of quantity (reduced production) e.g. a or b thalassaemia

Answer 11

Carriers of HbS are symptom free Carriage offers protection against falciparum malaria Sickle cell diseases arise in the homozygous state (SS) or in combined heterozygotes (SC or Sb thalassaemia)

Answer 12

Acute complications Painful crisis Sickle chest syndrome Stroke Chronic complications Renal impairment Pulmonary hypertension Joint damage

Answer 13

``` Transfusion Hydroxycarbamide – improves a lot of the complications Stem cell transplant Gene therapy Gene editing ```

Answer 14

Globin chain disorders resulting in diminished synthesis of one or more globin chains with consequent reduction in the haemoglobin Heterogeneous disorders of world wide distribution A variety of genetic lesions including deletions (mainly a thal) & mutations (b thal)

Answer 15

Thalassaemia Major Transfusion dependent Thalassaemia Intermedia Less severe anaemia and can survive without regular blood transfusions Thalassaemia Carrier/heterozygote Asymptomatic

Answer 16

Age at presentation: 6-12 months Clinical presentation with severe symptoms: failure to feed, listless, crying, pale Blood results: HB 40-70 g/l, mean corpuscular volume & mean corpuscular hemoglobin very low Blood film: large and small (irregular) very pale red cells, nucleated RBCs Hb F > 90% (neonatal sample) Ferritin normal

Answer 17

``` Regular transfusion Iron chelation Endocrine supplementation (fertility) Bone health Psychological support ``` Monitoring: Ferritin, Cardiac and Liver MRI, Endocrine testing, Gonadal function, Diabetes screening, Growth & puberty, Vit D, Calcium, PTH, Thyroid, Dexa scanning

Answer 18

Increase in body iron load. As there is no natural means for the body to eliminate the excessive iron, these patients inexorably develop a clinically worsening hemosiderosis. The excessive iron is deposited mainly in the liver and spleen, leading to liver fibrosis and cirrhosis. The excessive iron is also deposited in the endocrine glands and the heart, resulting in diabetes, heart failure and premature death. Death ultimately occurs, mainly due to cardiac hemosiderosis.

Answer 19

Carriage very common Because of distribution of a thalassaemia significant a thal disease (HbH or Barts Hydrops) confined to Eastern Med and Far East

Answer 20

Autosomal dominant conditions Spherocytosis & elliptocytosis most common Deficiency of red cell membrane proteins caused by a variety of genetic lesions Neonatal jaundice Mild to moderate haemolytic anaemia with occasional exacerbations during infection Predisposed to gallstones Folic acid and splenectomy in selected cases (mostly benign diseases)

Answer 21

Common upper respiratory tract infection in children Occurs in epidemics “slapped cheek syndrome” Leads to decreased RBC production Dramatic Hb drop in patients who already have reduced red cell lifespan.

Answer 22

Provides the fuel for the red cell Generates redox capacity to protect red cell Inherited enzyme deficiencies lead to shortened red cell lifespan from oxidative damage. G6PD deficiency and pyruvate kinase deficiency most common

Answer 23

Caused by a wide variety of mutations within G6PD gene Most asymptomatic X linked but women may also be affected Diagnosed by screening test for NADPH Crises characterised by haemolysis, jaundice, anaemia. Precipitated by broad beans, infection, drugs Usually self limiting Symptomatic patients rare.

Answer 24

A high concentration of red blood cells in your blood.

Answer 25

``` Reactive/Secondary Smoking Lung disease Cyanotic heart disease Altitude Epo/Androgen excess ``` Primary/Proliferative Polycythaemia Rubra Vera

Answer 26

An increase in circulating neutrophils above that expected in a healthy individual

Answer 27

Reactive Infection Inflammation Malignancy Primary CML

Answer 28

A higher-than-normal amount of lymphocytes, a subtype of white blood cells, in the body

Answer 29

Reactive Infection Inflammation Malignancy Primary CLL

Answer 30

Not enough platelets - reduced production

Answer 31

Reactive Infection Inflammation Malignancy Primary Essential Trombocythaemia

Answer 32

``` Not enough neutrophils Normal 1.7 – 6.5 Mild 1.0 – 1.7 Moderate 0.5 – 1.0 Severe <0.5 ``` Severe neutropaenia –major infection risk

Answer 33

Underproduction Marrow failure Marrow infiltration Marrow toxicity e.g. drugs Increased removal Autoimmune Felty’s syndrome Cyclical

Answer 34

Produced in bone marrow – arising from megakaryocytes (multinucleate, plentiful cytoplasm) Megakaryocyte fragments – break off, enter the blood stream Approx 4000 per megakaryocyte Regulated by thrombopoietin (made in the liver) Anucleate cell Lifespan 7-10 days Shorter when bleeding because they are consumed. Adhesion and aggregation to form platelet plug Main part of Primary haemostasis Removed by spleen

Answer 35

ABO HPA HLA Class I (not class II) Glycoproteins e.g. GP1a

Answer 36

Activated by Adhesion to collagen via GPIa, Adhesion to vWF via GPIb and IIb/IIIa Activation leads to - Release of α granules containing PDGF, Fibrinogen, vWF, PF4 - Dense granules - Membrane phospholipids activate clotting factors II (Prothrombin), V and X

Answer 37

) Platelets adhere to vascular endothelium via collagen & vWF (von Willebrand factor) 2) Binding of platelets to collagen stimulates cytoskeleton shape change within the platelets, and they ‘spread’ out 3) This increases their surface area and results in their activation, leading to the release of platelet granule contents including ADP, fibrinogen, thrombin and calcium. These components facilitate the clotting cascade ending with the production of fibrin. 4) Aggregation of platelets then occurs, which involves the cross-linking of activated platelets by fibrin 5) Activated platelets also provide a negatively charged phospholipid surface, which allows coagulation factors to bind and enhance the clotting cascade.

Answer 38

Number: FBC Appearance: blood film, drop of blood on the glass slide, dried, and stained. ``` Function: PFA (platelet function i.e. response to aggregating agents e.g. ADP, collagen Bleeding time (unreliable results) ``` Surface proteins: Flow cytometry – antibodies with fluorophores looking for platelet-specific surface proteins

Answer 39

``` Injury Vascular disorders Low platelets Abnormal platelet function Defective coagulation ```

Answer 40

``` Mucosal bleeding Epistaxis, gum bleeding, menorrhagia Easy bruising Petechiae, purpura Traumatic haematomas (inc subdural) ```

Answer 41

``` Production failure Congenital Acquired Drugs Marrow suppression Marrow failure Marrow replacement ``` Increased removal Immune Consumption Splenomegaly – aggregation of platelets Artefactual EDTA induced clumping

Answer 42

``` Congenital Platelet disorders Storage pool disorders Glanzmann Reduction/deficiency of GP IIb/IIIa Bernard Soulier Reduction/deficiency of GP1b=VW receptor von Willebrand disease ``` Acquired Uraemia Drugs – Aspirin and NSAIDs

Answer 43

Congenital thrombocytopenia Absent / reduced / malfunctioning megakaryocytes in BM Infiltration of bone marrow Leukaemia, metastatic malignancy, lymphoma, myeloma, myelofibrosis

Answer 44

Decreased production of platelets by the bone marrow due to low B12/folate, reduced TPO (e.g. liver disease), Methotrexate, chemotherapy, Toxins: e.g. Alcohol, Infections: e.g. viral (e.g. HIV) TB or Aplastic anaemia (auto immune). OR Dysfunctional production of platelets in bone marrow OR Increased destruction of platelets due to autoimmune, hypersplenism, drug-related immune destruction or consumption of platelets

Answer 45

IgG antibodies form to platelet and megakaryocyte surface glycoproteins Opsonized platelets are removed by reticuloendothelial system Primary: May follow viral infection / immunisation esp in children Secondary: Occurs in association with some malignancies, such as Chronic Lymphocytic Leukaemia (CLL) Infections e.g. HIV / Hep C

Answer 46

Investigations: No specific test Is there any underlying cause? Diagnosis of exclusion Treatment: Immunosuppression e.g. steroids / IVIG Treat underlying cause If bleeding – give platelets - but will disappear quickly Tranexamic acid inhibits breakdown of fibrin - Good for mucosal bleeding but NOT if urinary tract bleeding (clot retention)

Answer 47

An acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors.

Answer 48

Cytokine release in response to SIRS (Sepsis, trauma, pancreatitis, obstetric emergency, malignancy) Leads to Systemic activation of clotting cascade - May lead to micro-vascular thrombosis and organ failure - May lead to comsumption of platelets and clotting factors and bleeding

Answer 49

``` Underlying cause (usually sepsis or malignancy or obstetric causes) Thrombocytopenia, prolonged PT + APTT, low fibrinogen, high d-dimers +/- evidence of organ failure ```

Answer 50

``` Treat underlying cause Supportive provision of: - Platelets - FFP: contains clotting factors - Cryoprecipitate: contains fibrinogen and some clotting factors ```

Answer 51

Spontaneous platelet aggregation in microvasculature in brain, kidney, heart. Reduction in a protease enzyme – ADAMTS13 Acquired – due to antibodies against ADAMTS13 Failure to break down high molecular weight vWF multimers

Answer 52

Consumption of platelets Microangiopathic haemolytic anaemia - Rbc fragments (schistocytes) Renal / CNS / cardiac impairment Fever

Answer 53

Urgent plasma exchange (replaces ADAMTS 13 and removes antibody) Immunosuppression (reduce antibody level) Do NOT give platelets –increases thrombosis