Haematology Flashcards
What hormone stimulates the bone marrow to produce erythrocytes?
erythropoietin
What is the difference between adult and foetal haemoglobin?
Adult haemoglobin= 2a, 2b chains
Foetal haemoglobin = 2a, 2y chains
What is lymphoproliferative disease?
Neoplastic, clonal proliferation of lymphoid cells.
“a cancer of white blood cells “
typically affects lymph nodes
can be extranodal - bone marrow/liver/spleen/anywhere
What is a paraprotein?
Non-functional immunoglobulin produced by plasma cells in multiple myeloma.
What is myeloma?
A cancer of differentiated B-lymphocytes (plasma cells) in the bone marrow.
What is multiple myeloma?
A cancer of the plasma cells affecting multiple areas of the body
What are the features of multiple myeloma?
Calcium excess
Renal failure
Anaemia
Bone lytic lesions
Bleeding
Infection
What are the risk factors for multiple myeloma?
- Monoclonal gammopathy of undetermined significance (MGUS = plasma cells develop unusually in bone marrow)
- Family history of MM
- Radiation exposure
What is the pathophysiology of multiple myeloma?
- increase in bone resorption
- decrease in bone formation
- uncoupling of resorption and formation leading to rapid bone loss
What are the different types of multiple myeloma?
- monoclonal gammopathy of undetermined significance (MGUS)
- smouldering myeloma
- symptomatic myeloma
What is MGUS?
Monoclonal gammopathy of undetermined significance = excess of a single antibody or antibody components without other features of myeloma or cancer. May progress to myeloma.
What is smouldering myeloma?
Progression of MGUS with higher levels of antibody/antibody components. Premalignant and high risk of developing into myeloma.
What are the risk factors for myeloma?
Family history of myeloma
Radiation exposure
Older age
Male
Black african ethnicity
obesity
What are the key presentations of MM?
Old - 70+
C - hyperCalcaemia (increased bone resorption) -> bones, stones, abdo moans, and psychological groans
R - Renal failure (hypercalcaemia -> calcium oxalate renal stones), creatinine>173mmol/L
A - Anaemia (BM failure)
B - Bone lesions (BM failure = painful, new onset back pain in the elderly)
What are the investigations for MM?
FBC + blood film -> normocytic normochromic + increased ESR, Rouleaux formation (aggregation of RBCs together, abnormal)
GS: bone marrow biopsy >/=10% plasma cells
Urine dipstick indicating Bence Jones proteins (light chains)
What is the treatment for MM?
*Only treat symptomatic MM
- bisphosphonates (alendronate, clodronate, zoledronic acid or pamidronate)
- chemotherapy (bortezomid, thalidomide, dexamethasone)
- dialysis
- consider BM stem cell transplant
What is sickle cell anaemia?
An autosomal-recessive single gene defect in the beta chain of haemoglobin, which results in production of sickle cell haemoglobin (HbS).
What is the pathophysiology of sickle cell anaemia?
On the 6th codon of B-globin glutamic->valine causing irreversible RBC sickling.
Sickled RBCs are more fragile and have a decreased SA so are less efficient and die quicker with increased risk of sequestration.
What are the symptoms of SCA?
general anaemia + jaundice
+ complications:
- acute sickle crisis = vessel occluded, extremely painful and medical emergency (can be in pulmonary vessel = acute chest crisis –> resp. distress)
- splenic sequestration - can cause autosplenectomy (basically non-functional spleen)
- osteomyelitis (caused by salmonella)
What are the investigations for SCA?
- Newborns are screened in heel prick test
- FBC + blood film = normocytic normochromic w/ increased reticulocytes, sickled RBCs+ Howell Joly bodies (nuclear remnants found in the RBCs of patients with reduced or absent splenic function)
- Hb electrophoresis
What is the management of SCA?
prevent complications whenever possible (stay warm + hydrated, vaccinations, monitoring, regular blood transfusion, hydroxycarbamide - ↑HbF
- only curative therapy = bone marrow transplant (signifciant risks)
- iron chelation (treats iron overload)
Acute attacks: IV fluid + analgesia + O2
What is splenic sequestration in SCA?
Occurs when blood cells get stuck in the spleen and block the passage of platelets out of the spleen. This can result in 90% of circulating platelets becoming sequestered in the spleen and is a medical emergency.
What is thalassaemia?
Overarching term for several conditions which result in lack of haemoglobin production.
What is alpha thalassaemia?
Abnormality of a-globin gene
- less common than b thalassaemia
- 4 genes on chromosome 16
- deletions, associated with HbH (abnormal isoform where b-chain tetramers form)
What is beta thalassaemia?
Abnormality of b-globin gene
- 2 genes on chromosome 11
- mutations, normal Hb isoforms
- just deletion of b-chains
What are the clinical classifications of beta thalassaemia?
- thalassaemia major - transfusion dependent
- thalassaemia intermedia - less severe and can survive without regular blood transfusions
- thalassaemia carrier - asymptomatic
What are the risk factors for thalassaemia?
- FH
- More common in people of African, Mediterranean and Southeast Asian descent
What are the key clinical manifestations of b-thalassaemia?
variable depending on number of mutations:
- general anaemia
- chipmunk facies (enlarged forehead and cheekbones)
- hepatosplenmegaly
- failure to thrive
What are the investigations for thalassaemia?
FBC, peripheral smear, reticulocyte test
genetic testing to confirm diagnosis
XR skull, long bones, abdo US
What is the treatment for thalassaemia?
Bone marrow stem cell transplant only curative option
Regular blood transfusions needed for survival (complications: iron overload, iron chelation)
What is Hodgkin’s lymphoma?
Cancer of the lymph nodes where white blood cells grow out of control, causing swollen lymph nodes and growths throughout the body.
What are the types of Hodgkin’s lymphoma?
- Nodular sclerosis HL
- Mixed cellularity HL
- Lymphocyte-depleted HL
- Lymphocyte-rich HL
What are the risk factors for HL?
- History of Epstein-barr virus infection (aka glandular fever)
- FH of hodgkin’s lymphoma
- Young adults from higher socio-economic class
- HLA types
- More commonly diagnosed in older people and teenagers
- HIV infection
What are the key presentations of Hodgkin’s lymphoma?
B symptoms (=fever, night sweats, unintentional weight loss)
Painless rubbery lymphadenopathy (painful after drinking alcohol)
What are the investigations for HL?
- Lymph node biopsy (Reed Sternberg +ve = large abnormal lymphocytes)
- CT/MRI chest, abdo, pelvis for staging
What is the treatment for HL?
ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine)
Radiotherapy
What are the 4 stages in Ann Arbour lymphoma staging?
1 - Single lymph node
2 - 2 ≤ lymph nodes on same side of diaphragm
3 - Lymph nodes on both sides of diaphragm
4 - Extra-nodal organ spread
What is the distinguishing factor between Hodgkin’s and Non-Hodgkin’s lymphoma?
The presence of Reed-Sternberg cells in Hodgkin’s lymphoma
What is Non-Hodgkin’s lymphoma?
A group of lymphomas e.g. Burkitt Lymphoma (associated with EBV, malaria and HIV), MALT lymphoma (Mucosa-associated lymphoid tissue, associated with H.pylori infection), Diffuse large B cell lymphoma (65+, rapid-growing)
What are the risk factors for NHL?
HIV
EBV
H.pylori
Hepatitis B or C
Exposure to pesticides
Family History
What is the management for NHL?
watchful waiting
chemotherapy (R-CHOP)
radiotherapy
monoclonal antibodies
stem cell transplant
What is R-CHOP chemotherapy?
An immunochemotherapy regimen consisting of Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Vincristine (Oncovin) and Prednisone used to treat both indolent and aggressive forms of non-Hodgkin lymphoma.
What is indolent lymphoma?
Form of NHL which is slow growing and only presents with symptoms at an advanced stage.
What is ABVD chemotherapy?
ABVD is the name of a chemotherapy combination that includes doxorubicin, bleomycin, vinblastine and dacarbazine. It is a treatment for Hodgkin lymphoma
What is leukaemia?
cancer of a particular line of the stem cells in the bone marrow resulting in unregulated production of certain types of blood cells.
What are the 4 main types of leukaemia?
Acute myeloid leukaemia
Chronic myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic lymphocytic leukaemia
What are the progressive ages of leukaemias?
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)
What is acute myeloid leukaemia?
A heterogeneous clonal malignancy characterised by immature myeloid cell proliferation and bone marrow failure.
What are the risk factor for AML?
- Myelodysplastic Syndromes
- Most patients with chronic myeloid leukaemia eventually develop a blast phase indistinguishable from AML
- Radiation
- Some congenital disorders (Down’s, Bloom’s syndrome, congenital neutropenia)
What are the key presentations of AML?
- Anaemia (SOB, light-headedness, fatigue, worsening angina)
- Neutropenia (frequent infections)
- bleeding
- splenomegaly
- bone pain
What are the investigations for AML?
FBC + blood film (key feature Auer rods in abnormal leukocytes)
Bone marrow aspirate
Trephine biopsy
CXR
What are some differential diagnoses for AML?
- B12/folate or mixed haematinic deficiency
- Infection (e.g. retroviral disease, herpesvirus)
- Medications
- Autoimmune
- Liver disease (e.g. cirrhosis)
What are the 2 phases of chemotherapy treatment for AML?
induction: cytarabine, daunorubicin and gemtuzumab ozogamin
post-remission consolidation: chemotherapy with stem cell replacement therapy
What is chronic myeloid leukaemia?
A malignant clonal disorder of the haematopoietic stem cell resulting in marked myeloid hyperplasia of the bone marrow.
What is the cause of CML?
Caused by characteristic cytogenetic change which is the translocation of genes between chromosome 9 and 22 called the Philadelphia chromosome (t(9:22))
This causes dysregulation of haematopoiesis arises due to a BCR-ABL fusion gene that causes tyrosine kinase to be irreversibly switched on resulting in an abnormal expansion of myeloid cells in the bone marrow and peripheral blood.
What are the 3 phases of CML?
Chronic phase = often asymptomatic and is often diagnosed incidentally with a raised white cell count.
Accelerated Phase = occurs where the abnormal blast cells take up 10-20% of the cells in the bone marrow and blood. Patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.
Blast phase = even higher proportion of blast cells in the blood (>30%) causing severe symptoms and pancytopenia, is often fatal.
What are the key presentations of CML?
Splenomegaly
SOB on exertion
Epistaxis due to thrombocytopenia or abnormal platelet function
Arthralgia
Sternal tenderness
What are the investigations for CML?
FBC (pancytopenia but granulocytosis)
BM Biopsy (increased granulocytes)
Genetic testing (philadelphia chromosome)
What is the management for CML?
Chemotherapy + Imantinib (Tyrosine kinase inhibitor)
Consider allopurinol (lowers uric acid levels)
What is ALL?
Malignant change of one of the lymphocyte precursor cells - causes acute proliferation of a single type of lymphocyte (usually B lymphocytes) which leads to replacement of other cell types being created in the bone marrow ⇒ pancytopenia.
What are the risk factors for ALL?
Down’s syndrome (30x risk)
Radiation exposure
Smoking
Viral infections
History of malignancy
Poor maternal diet
What are the key presentations for ALL?
General leukaemia symptoms (fatigue, failure to thrive, fever, pallor, petechiae, abnormal bleeding, lymphadenopathy, hepatosplenomegaly)
What are the investigations for ALL?
FBC = pancytopenia
Blood film = ↑lymphoblasts
BM biopsy = ≥20% lymphoblasts
Immunofluorescence = TdT +ve lymphoblasts (terminal deoxynucleotidyl transferase)
What is CLL?
Chronic proliferation of a single type of well-differentiated lymphocyte (usually B-lymphocytes).
What are the risk factors for CLL?
65+
Male
White ethnicity
Family Hx of CLL
What is Richter’s transformation?
The conversion of Chronic Lymphocytic Leukaemia into high grade Non-Hodgkin’s lymphoma (large B cell lymphoma)
What are the symptoms of CLL?
Often asymptomatic but can present with infections, anaemia, bleeding and weight loss
Non-tender lymphadenopathy
Hepatoplenomegaly
What are the investigations for CLL?
FBC - pancytopenia (except lymphocytes)
Blood film (smear/smudge cells which occur during the blood fil prep where aged/fragile WBCs rupture and leave a smudge on the film)
Immunoglobulins = Hypogammaglobulinemia (B cells proliferate but don’t differentiate to plasma cells)
What is the treatment for CLL?
progressive = chemo, palliative (if old)
Consider allopurinol
IVIg for hypogammaglobulinemia
What are myelodysplastic syndromes?
A group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells.
- Bone marrow cells fail to make adequate numbers of healthy blood cells (cytopenias)
- Abnormal cells crowd out remaining normal cells
- Variable risk of progression to Acute Myeloid Leukaemia
What is the treatment for ALL?
Chemotherapy (+consider allopurinol)
What are the clinical manifestations of MDS?
Low blood counts:
- Red cells → fatigue, shortness of breath, lightheadedness
- White cells → increased risk of frequent and/or severe infections
- Platelets → bleeding/bruising
Neutropenia (low neutrophils)
What are the investigations for MDS?
FBC + blood film
haematinic bloods
Bone marrow aspirate
trephine biopsy
Peripheral blood film
What are constitutional (B) symptoms?
- night sweats
- fever
- unintentional weight loss (loss of >10% body weight over 6 months)
What is the MCV test?
Mean cell (corpuscular) volume = cell size
macrocytic = cells larger than normal
microcytic = cells smaller than normal
normocytic = cell size within normal range (80-98fl)
What is the MCH test?
Mean cell haemoglobin = amount of haemoglobin in each cell
Hypochromic = less haemoglobin in each cell than normal
Normochromic = normal amount of haemoglobin (27-33pg)
What are the causes of microcytic anaemia?
T - Thalassaemia
A - Anaemia of chronic disease
I - Iron deficiency anaemia
L - Lead poisoning
S - Sideroblastic anaemia
What are the causes of normocytic anaemia?
A - Acute blood loss
A - Anaemia of Chronic Disease
A - Aplastic Anaemia
H - Haemolytic anaemia
H - Hypothyroidism
What are the causes of megaloblastic macrocytic anaemia?
Folate deficiency
B12 deficiency
What are the causes of normoblastic macrocytic anaemia?
- Alcohol
- Reticulocytosis (usually from haemolytic anaemia or blood loss)
- Hypothyroidism
- Liver disease
- Drugs such as azathioprine
What is anaemia?
A condition in which the number of red blood cells or the haemoglobin concentration within them is lower than normal.
Defined as Hb <120g/l in females and <140 g/l in males
What are the normal serum haemoglobin levels?
female 110-147g/l, male 131 – 166g/l
What is the normal RBC count in blood?
men – 4.0 to 5.9 x 1012/L. women – 3.8 to 5.2 x 1012/L.
What are the symptoms of anaemia?
- Tiredness
- SOB
- headaches
- dizziness
- palpitations
- worsening of other conditions like angina, heart failure or peripheral vascular disease
What are the signs of anaemia?
- pale skin
- conjunctival pallor
- tachycardia
- raised respiratory rate
What are the investigations for anaemia?
Haemoglobin
Mean cell volume (MCV)
B12
Folate
Ferritin
Blood film
Oesophago-gastruduodenoscopy (OGD) and colonoscopy to investigate for a gastrointestinal cause of unexplained iron deficiency anaemia (for suspected GI cancer)
Bone marrow biopsy if cause is unclear
What are the causes of iron deficiency anaemia?
Blood loss = most common cause in adults
Dietary insufficiency is the most common cause in growing children
Poor iron absorption
Increased requirements during pregnancy
Coeliac/Crohn’s diseases
What are the risk factors for iron deficiency anaemia?
Pregnancy
Vegetarian /vegan diet
Menorrhagia
Hookworm infestation
CKD
Coeliac disease
Gastrectomy
NSAIDs
What are the key presentations of iron deficiency anaemia?
fatigue , dyspnoea on exertion, pica (abnormal craving for non-food substances e.g. soil, clay), restless leg syndrome, nail changes (e.g. koilonychya), dysphagia, impaired muscular performance, dyspepsia, pallor, hair loss
What are the investigations for IDA?
Transferrin Saturation = Serum Iron/Total iron binding capacity (15-50%)
Ferritin (41-400ug/L)
Serum iron (12-30 umol/L)
Total iron binding capacity (45-80 umol/L)
What is the management for IDA?
Treat underlying cause and correct anaemia:
- blood transfusion
- iron infusion
- oral iron e.g. ferrous sulphate 200mg TD
What is sideroblastic anaemia?
defective Hb synthesis within mitochondria where there is increased iron but the body is unable to use it in haemoglobin synthesis.
What are the causes of sideroblastic anaemia?
- alcoholism
- B6 deficiency
- lead poisoning
- congenital
What are the treatment aims for sideroblastic anaemia?
- remove toxic agents
- administration of pyridoxine (vitamin B6), thiamin or folic acid
- bone marrow or liver transplantation
What is shown in iron studies of patients with sideroblastic anaemia?
Increased serum iron, ferritin and transferrin
Decreased TIBC (total iron blood capacity)
What are the causes of neutropenia?
infection (EBV, HIV, Hep B/C)
drugs (phenytoin, antipsychotics)
endocrine
malignancy (myeloma)
autoimmune
excess alcohol + liver disease
What are the causes of neutrophilia?
infection (mc) (bacterial, VZV, HSV)
drugs (steroids)
malignancy (leukaemia, lymphoma)
rheumatoid arthritis
gout
hypoxia
What is the normal neutrophil count in the blood?
2-7.5 x 10^4/L
>7 = neutrophilia, <2 = neutropenia
What are the causes of lymphocytopenia?
drugs (steroids)
infection (post-viral)
malignancy
renal/hepatic impairment
SLE, RA
anorexia nervosa
What are the causes of lymphocytosis?
infection (EBV, CMV, pertussis)
stress
vigorous exercise
malignancy
post splenectomy
What is the normal lymphocyte count in the blood?
1.3-3.5 x10^4/L
>3.5 = lymphocytosis, <1.3 = lymphocytopenia
WHat are the causes of thrombocytopenia?
viral infection
drugs (NSAIDs, heparin, digoxin, PPIs)
alcohol
malignancies
liver + renal disease
aplastic anaemias
SLE
What are the causes of thrombocytosis?
reactive (infection, inflammation, haemorrhages, post-surgery)
malignancies
splenectomy
iron deficiency
What is the normal platelet count in the blood?
150-400 x10^4/L
>400 = thrombocytosis, <150 = thrombocytopenia
What is G6PDH deficiency?
X-linked recessive enzymopathy causing destruction of RBCs which leads to anaemia
What are the risk factors for G6PDH Deficiency anaemia?
- male
- african-american or middle-eastern descent
- family history
What is the pathophysiology of G6PDH deficiency anaemia?
The G6PD gene is involved in the production of G-6-P dehydrogenase enzyme which helps process carbohydrates and protect RBCs from reactive oxygen species by preventing toxic build up in RBCs.
Mutation of this gene can therefore result in accumulation of ROSs causing RBCs to be destroyed faster than the body can replace them ⇒ haemolytic anaemia.
Symptoms are often triggered by taking sulfa drugs (antibacterials, antifungals, diuretics, anticonvulsants), an infection or by eating certain foods such a legumes.
What are the key presentations of G6PDH Deficiency Anaemia?
Most often asymptomatic but once triggered:
Fatigue
Jaundice
SOB
Rapid heart rate
Dizziness
Dark yellow/orange urine
What are the investigations for G6PDH Deficiency Anaemia?
G6PD Test
FBC, bilirubin, reticulocyte count, serum aminotrasnferases, peripheral blood smear
What is seen on a blood film with G6PDH deficiency?
irregularly contracted cells
bite cells (membrane indentation)
Reticulocytosis
Low levels of G6PD enzyme
What is the management for G6PDH Deficiency Anaemia?
Involves avoiding certain foods and medication which trigger the condition.
Symptom-specific treatment e.g. phototherapy for jaundice
Blood transfusions
What is pernicious (B12 deficiency) anaemia?
An autoimmune condition where antibodies form against the parietal cells or intrinsic factor. A lack of intrinsic factor prevents the absorption of vitamin B12 and the patient becomes vitamin B12 deficient.
What are the risk factors for pernicious anaemia?
Old age
Hx of gastric surgery
Vegan/strict vegetarian diet
Chronic GI disease (Crohn’s, coeliac)
Medicine (PPIs, metformin)
Ataxia
Pallor
Petechiae
Scandinavian or Northern European descent
What are the causes of pernicious anaemia?
Common causes of pernicious anaemia include a weakened stomach lining (atrophic gastritis, autoimmune condition in which the body’s immune system attacks the parietal cells or the intrinsic factor protein itself)
What are the symptoms of pernicious anaemia?
Paraesthesias (pins and needles)
Tiredness
Feeling faint
SOB
Ataxia
Pallor
Petechiae
Palpitations
Altered taste
Dysphagia
What are the investigations for pernicious anaemia?
Anti-intrinsic factor antibody test
Parietal cell antibodies
FBC
What is the management of pernicious anaemia?
Dietary B12 deficiency can be treated with oral replacement with cyanocobalamin unless deficiency is severe.
If problem is with absorption rather than intake treat with hydroxocobalamin
B12 deficiency should always be treated before folate deficiency if both are present.
What is folate deficiency anaemia?
Anaemia due to lack of folic acid in the blood which is needed for RBC production.
What are the causes of folate deficiency?
Malnutrition
malabsorption ,
Pregnancy
Trimethoprim + methotrexate (dihydrofolate reductase inhibitors which cause reduced folate production)
Alcohol
What are the key presentations of iron deficiency anaemia?
general anaemia symptoms (fatigue, pallor, feeling faint, SOB)
angular stomatitis + gastritis
What are the investigations for folate deficiency anaemia?
FBC + blood film
What is the management for folate deficiency anaemia?
Dietary advice (green leafy veg, brown rice)
Folate supplements
what is hereditary spherocytosis
Inherited abnormality of RBCs caused by defects in structural membrane proteins which causes haemolytic anaemia.
what are the risk factors for hereditary spherocytosis?
Fhx of splenectomy, anaemia, jaundice or HS
Most common in northern-europeans
What is the pathophysiology of hereditary spherocytosis?
The RBC defects result in loss of surface membrane area relative to volume so the red-cells becomes spherical and less flexible. They are fragile and the spleen selectively removes and destroys the abnormal spherocytes leading to hyperbilirubinemia, an elevated reticulocyte count and splenomegaly.
The severity of the membrane defect is related to the clinical severity and symptoms.
What are the key presentations of hereditary spherocytosis?
General anaemia
Neonatal jaundice
Splenomegaly
Gall stones (50%)
What are the investigations for hereditary spherocytosis?
FBC + blood film = normocytic normochromic + increased reticulocytes + spherocytes
What is the management for hereditary spherocytosis?
Splenectomy (to decreased extravascular haemolysis)
Folate supplements
Blood transfusion
What is polycythaemia vera?
A clonal haematopoietic disorder characterised by erythrocytosis and often thrombocytosis, leukocytosis and splenomegaly.
What is the cause of polycythaemia vera?
Mutations in the bone marrow haematopoietic stem cells (JAK2V617 mutation in 95% of cases) result in the activation of biochemical pathways involved in erythropoietin receptor signalling. This results in a trilineage expansion of morphologically normal RBCs, WBCs and platelets.
What are the key presentations of polycythaemia vera?
Itchy after a bath
Burning in fingers + toes (erythromegalgia)
Reddish plethoric complexion (puffy face)
Blurred vision/headache
Hepatosplenomegaly
What are the investigations for polycythaemia vera?
FBC (raised Hg >185g/l in men, >!65g/l in women)
Genetic test; JAK2V617
What is the management for polycythaemia vera?
Non-curative, treatment to maintain normal blood count
Regular venesection (removes blood cells)
Low risk disease - aspirin BD
Chemotherapy is used to control the disease
High risk disease - add hydroxycarbamide 500mg - arterial thrombosis history → aspirin BD, venous thrombosis history → + systemic anticoagulation
What is thrombocytopenia?
Low platelet count of various causes.
Platelet count < 50 x10^9/L
What is Immune thrombocytic purpura?(ITP)
Autoimmune platelet destruction (IgG)
Also known as autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura, primary thrombocytopenic purpura
What is the pathophysiology of ITP?
Antibodies are created against platelets causing an immune response against platelets ⇒ destruction of platelets and low platelet count (thrombocytopenia)
T1: children 2-6yrs, post viral infection (acute + severe)
T2: adult women with malignancy, HIV, other autoimmune condition (chronic + mild)
What are the key presentations of ITP?
Purpuric rash
Easy bleeding
Menorrhagia
Otherwise well systemically
What are the investigations for ITP?
FBC + blood film, (thrombocytopenia + ↑BM megakaryoblasts)
What is the management for ITP?
Prednisolone + IVIg (decrease splenic platelet destruction)
Rituximab (monoclonal antibody against B cells)
Splenectomy
What is TTP?
Thrombotic Thrombocytopenic Purpura = Development of tiny blood clots in small vessels which use up platelets leading to thrombocytopenia. Described as a microangiopathy.
What is the cause of TTP?
Deficiency in the ADAMTS13 protein can be due to an inherited genetic mutation or due to an autoimmune disease where antibodies are created against the protein
What are the risk factors for TTP?
Adult female
Malignancy
HIV
Autoimmune
What is the pathophysiology of TTP?
The blood clots develop due to a problem with a specific protein called ADAMTS13 which normally inactivates vonWIllebrand factor and reduces platelet adhesion to vessel walls and clot formation.
A shortage in this protein leads to vonWillebrand factor overactivity and the formation of blood clots in small vessels which uses up platelets and leads to thrombocytopenia.
The blood clots in the small vessels break up red blood cells leading to haemolytic anaemia.
What are the key presentations of TTP?
Purpuric rash
Generally unwell
Menorrhagia
AKI
Fever
Haemolytic anaemia
Neurological symptoms
What are the investigations for TTP?
FBC + blood film (thrombocytopenia, schisocytes (=fragmented RBCs), microangiopathic haemolytic anaemia)
What is the management of TTP?
Plasmapheresis (removes extra antibodies and abnormal proteins from blood)
Prednisolone + Rituximab
What causes prolonged aPTT and PT?
- deficiency of factors I, II, X, V
- severe liver disease (↓II, IX, X)
- vitamin K deficiency
- warfarin toxicity
What causes prolonged aPTT?
defieicney of factors VIII, IX, XI, XII
von Willebrand factor deficiency (severe)
haemophilia A (factor VIII deficiency)
haemophilia B (factor IX deficiency)
factor VIII inhibitor
lupus anticoagulant
What is prolonged TT and what causes it?
Thrombin time, measures final step of coagulation cascade (fibrinogen–> fibrin)
Caused by:
direct thrombosis inhibitors
hypofibrinogenaemia
Which bleeding disorders do not affect aPTT or PT?
platelet issues
von Willebrand disease
Ehlers-Danlos syndrome
Scurvy
Hereditary haemorrhagic telangiectasia
osteogenesis imperfecta
steroids - weakens vessels
What are the causes of prolonged PT?
factor VII deficiency
liver disease
vitamin K deficiency
warfarin use
