Blood Disorders Flashcards
(146 cards)
1
Q
What are the constituents of a red cell count?
A
Hb MCV Reticulocyte count Red cell count Haematocrit MCH
2
Q
What is the reticulocyte count? What does it mean if its high?
A
The concentration of immature RBCs
High: increased blood loss and haemolytic anaemia because the bone marrow works harder to replace lost cells
3
Q
What is the haematocrit?
A
Volume percentage of RBCs in the blood
4
Q
What causes a microcytic anaemia?
A
Iron deficiency anaemia Thalassemia Sideroblastic anaemia (production of ringed abnormal RBCs)
5
Q
What causes a normocytic anaemia?
A
Acute blood loss
Haemolytic anaemia
Chronic disease
Multiple myeloma
6
Q
What causes a macrocytic anaemia?
A
B12/folate deficiency Alcohol Reticulocytosis Liver disease Pregnancy
7
Q
What is a physiological cause of normocytic/macrocytic anaemia?
A
Pregnancy
8
Q
What tests are included in a haematinics study?
A
B12/folate
Ferritin
9
Q
What does a high/low ferritin tell us?
A
High - not useful as ferritin is an acute phase protein so rises with any inflammation
Low - iron deficiency
10
Q
What causes iron deficiency anaemia? What are the signs?
A
- Chronic blood loss (menstrual/GI/urinary)
- Increased demand
- Decreased absorption (coeliacs - do tTg), gastrectomy)
- Poor intake
SIGNS - koilonychia, angular stomatitis, glossitis
11
Q
How is iron deficiency anaemia treated?
A
Ferrous sulphate tablets
Transfusion if Hb<70
12
Q
How is B12 absorbed?
A
Binds to intrinsic factor, allowing it to be observed in the terminal ileum
13
Q
What causes B12 anaemia?
A
- Pernicious anaemia
- Malabsorption
- Not enough meat/fish etc
14
Q
What causes folate deficiency anaemia?
A
- Increased requirements
- Dietary (not enough green veg)
- Malabsorption
- Drugs (trimethoprim, phenytoin)
15
Q
What are some heritable causes of haemolytic anaemia?
A
Haemoglobinopathies: sickle cell
Membrane defects: hereditary spherocytosis, elliptocytosis
Enzyme defects: G6PD deficiency, pyruvate kinase deficiency
16
Q
What are some acquired causes of haemolytic anaemia
A
Autoimmune (DAT+) - drug induced
Non-immune: DIC, TTP, infection
17
Q
What is Coombs test for?
A
Autoimmune haemolytic anaemia - DAT direction antiglobulin test
18
Q
What is polycythemia?
A
Increased number of RBCs in the blood
19
Q
What are the primary and secondary causes of polycythemia?
A
Primary - polycythemia vera (all cell lines increased)
Secondary - increased epo or chronic hypoxia (just RBC increased)
20
Q
What causes a high/low neutrophil count?
A
High - bacterial infection, inflammation, steroids, malignancy, stress
Low - chemo, agranulocytosis 4Cs (carbamazepine, clozapine, colchicine, carbimazole)
21
Q
What causes a high/low lymphocyte count?
A
High - viral infection, CLL, chronic infections
Low - viral infection, HIV, chemo, bone marrow failure
22
Q
What causes a high/low monocyte count?
A
High - bacterial infection, autoimmune disease, leaukemia
Low - acute infection, steroids, leukemia
23
Q
What causes a high/low eosinophil count?
A
High - allergy, parasite, drug reactions
Low - n/a
24
Q
What causes a high/low basophil count?
A
High - leukaemia, hypersensitivity, myeloproliferative disorders
Low - n/a
25
What causes thrombocytopenia?
Decreased production - bone marrow failure, megaloblastic anaemia
Increased destruction - DIC/TTP/ITP/SLE/CLL/viruses/drugs
26
What causes thrombocythemia?
Primary - myeloproliferative disorders
| Secondary - bleeding, inflammation, infection, malignancy
27
What is a myeloproliferative disorder?
A group of neoplastic disorders involving the bone marrow cells that produce RBCs, platelets or fibroblasts (everything except WBCs)
1. Essential thrombocythemia
2. Chronic myeloid leukemia
3. Polycythemia vera
4. Myelofibrosis
28
What is essential thrombocythemia and how does it present?
Overproduction of platelets by bone marrow
| - asymptomatic, headache, dizziness, bruising, thrombosis
29
What do investigations show for ET?
a) bloods
b) genetics
B: Isolated rise in platelets
G: JAK2, CALR or MPL mutation
30
How is ET treated?
1. Aspirin to reduce clot risk
2. Cytoreductive surgery
3. Hydroxycarbamide
31
What is chronic myeloid leukemia and how does it present?
Neoplastic disease of mature myeloid cells in the bone marrow, involving basophils, eosinophils and neutrophils
- incidental finding, fever, night sweats, splenomegaly, weight loss, bleeding, petechia, gout, hyper-viscosity syndrome
3 clinical phases:
1. Chronic
2. Accelerated
3. Blast crisis (symptoms of AML)
32
What do investigations show for CML?
a) bloods
b) cytogenetics (most important test)
a) increased myeloid cells, myeloblasts
| b) translocation(9:22) involving the ABL:BCR genes - PHILADELPHIA CHROMOSOME
33
How is CML treated?
- Tyrosine kinase inhibitor (Imatinib)
- PCR monitoring of BCR:ABL
- Stem cell transplant
34
What are the side effects of Imatinib?
Pleural effusion, rash, cramps, vomiting, oedema
35
What is polycythemia vera and how does it present?
Overproduction of RBC by the bone marrow cells, causing the blood to thicken
- thrombosis, splenomegaly, often asymptomatic
- itch particularly after a hot shower
36
How is polycythemia investigated?
a) bloods
b) genetics
a) all cell lines high, low epo
| b) JAK2 mutation
37
How is polycythemia vera treated?
1. Aspirin to reduce clot risk
2. Cytoreductive surgery
3. Hydroxycarbamide
38
What is multiple myeloma and how does it present?
```
Neoplastic disease of plasma cells (B cells that produce antibodies.
CRAB presentation
- Calcium increased
- Renal impairment
- Anaemia
- Bony lesions
```
BACK PAIN!!!
These are due to paraprotein clogging up various sites
39
What ethnicity have a higher proportion of patients with multiple myeloma?
African descent
40
What is the pathophysiology of multiple myeloma?
Plasma cells proliferate and produce paraprotein, a faulty monoclonal antibody.
41
How is multiple myeloma diagnosed?
Serum paraprotein (immunoglobulin electrophoresis)
Serum free light chain blood test
Blood film rouleax - increased plasma viscosity due to overproduction of immunoglobulins
42
How is multiple myeloma treated?
- Chemo
- Bisphosphonates
- Stem cell transplant
- Stop nephrotoxic drugs
43
What are the symptoms of iron deficiency?
Fatigue, leg cramps and craving ice
44
What are the symptoms of iron overload/haemochromatosis?
Chondrocalcinosis, iver cirrhosis, diabetes, cardiomyopathy, arthritis 'bronzed diabetes'
45
What is the pathophysiology of primary haemochromatosis?
Mutation in HFE gene, so hepcidin isnt produced and too much iron is absorbed from the blood.
It is then stored in the liver and heart, where it causes cirrhosis and cardiomyopathy
46
What causes secondary haemochromatosis?
Chronic haemolysis, multiple transfusion, excess dietary
47
How is haemochromatosis treated? What investigation should you do to look for complications?
1. Phlebotomy
2. DFO/DFP (bind iron)
MRI for liver and heart
48
What is myelofibrosis?
Bone marrow disorder characterised by excessive fibrosis due to proliferation of an abnormal clone of haematopoietic stem cells
49
What are the primary and secondary types of myelofibrosis?
Primary - idiopathic
| Secondary - develops from PV or ET (other myeloproliferative disorders)
50
What are the symptoms of myelofibrosis?
MASSIVE SPLENOMEGALY, bone pain, fatigue, bruising, sweats
51
What investigations should be done in myelofibrosis
a) bloods
b) blood film
c) bone marrow biopsy
Bloods - pancytopenia OR pancythemia
Blood film - tear drop poikilocytes/dacrocytes and nucleated RBCs
Biopsy - collagen fibrosis, JAK2/MLP/CALR mutation
52
How is myelofibrosis managed?
Generally incurable, except for stem cell transplant
Symptomatic treatment - transfusion, allopurinol, splenectomy, folic acid, JAK2 inhibitors
53
What are the symptoms of hereditary spherocytosis?
Splenomegaly, jaundice and fatigue, associated with cholecytisis
54
What is the pathophysiology of hereditary spherocytosis?
Patients have abnormally shaped but functioning inherited erythrocytes. The spleen attacks them (and becomes massive), causing anaemia with a high reticulocyte count
55
What would you expect from macrocytic anaemia and pancytopenia?
B12/folate deficiency
56
How is B12 deficiency managed?
If no intrinsic factor is present either, patient will need lifelong IM B12 (oral wont work due to lack of IF)
57
What factors are involved in the extrinsic pathway, and how is this measured?
7
| PTT
58
What factors are involved in the intrinsic pathway, and how is this measured?
8,9,11,12
| APTT
59
What factors are vitamin K dependent?
2, 7, 9, 10
60
Describe the process of clot formation
1. Vasconstriction of the blood vessel
2. Platelet activation and plug formation - granules release ADP, TXA2
3. Endothelial trauma causes VWF release from WP bodies, this creates a bridge between the platelet plug and collagen in the vessel wall, allowing it to attach
4. This activates the clotting cascade
4. Production of a fibrin mesh which stabilises the clot
61
What features would you expect in a history of a patient with a bleeding disorder?
- Bleeding from minor wounds
- Bleeding after surgery
- Heavy periods
- Bruising
- Gum bleeding
62
What is a correction study?
A blood test performed if you have a long APTT/PTT. Add normal plasma to the blood sample:
- If APTT/PTT corrects - it is a clotting factor deficiency, do an assay
- If it doesnt correct - the blood has an abnormal factor inhibitor
63
Which is the most common clotting factor inhibitor found in the blood?
Lupus anticoagulant
64
What are the symptoms of haemophilia?
Bleeding, arthropathy (bleeding into joints)
65
What is the pathophysiology of haemophilia A?
X linked recessive deficiency in factor 8, causing high APTT.
NB - 30% are do novo mutations so dont always expect a family history
66
What is the pathophysiology of haemophilia B?
X linked recessive deficiency in factor 9, causing high APTT
67
How should haemophilia be treated?
- Recombinant factor 8/9
- Desmopressin
- Analgesia and joint immobilisation
- Physio
- Avoid aspirin/NSAIDS/heparin
68
What is the pathophysiology of Von Willebrand Disorder?
Autosomal deficiency in VWF which usually binds:
- platelets
- factor 8
69
What are the symptoms of VWF disorder?
Mucocutanoues bleeding, bruising
70
What are the the 3 types of Von Willebrand Disorder?
Type 1 - asymptomatic (normal VWF not enough)
Type 2 - mild symptoms (abnormal VWF)
Type 3 - Severe, no VWF at all, may have internal bleeding
71
How is VWF diagnosed?
- Do VWF levels and functionality with a Gp1b assay
- Reduced ristocetin cofactor activity
- Reduced factor 8, increased APTT
Sometimes bloods won't show anything!
72
How is VWF managed?
- Desmopressin
- Pooled plasma concentrates containing VWF
Often treatment only needed before surgery/dental procedures
73
What is the most common bleeding disorder?
Von Willebrand Disorder
74
What is the mechanism behind excessive bleeding in renal disease?
Uraemia leads to reduced platelet aggregation and associated bleeding
75
What is the mechanism behind excessive bleeding in liver disease?
Impaired production of clotting factors
76
What is haemorrhagic disease of the newborn?
All babies are born vitamin K deficient so there is impaired production of 2 7 9 and 10 and protein C/S
77
What is DIC?
Widespread activation of coagulation from release of procoagulants. Eventually these factors get used up, leading to bleeding
78
How is DIC diagnosed?
Low platelets
High PT/APTT
High fibrinogen degradation products
High D dimer
79
What causes DIC?
Sepsis
Malignancy
Obstetric catastrophe
Major haemorrhage
80
How is DIC managed?
- Treat underlying cause
| - Resuscitate with red cells, plasma, platelets, cryoprecipitate and blood warmers
81
What is cryoprecipitate rich in?
Factor 8
82
How is the clotting cascade initiated?
Factor 7 and tissue factor form a complex which activates factor 10.
83
What is a lymphoma?
A neoplastic disorder of mature lymphocytes in lymphoid tissue, in which abnormal lymphocytes collect in lymph nodes, particularly in the armpits, groing and neck.
84
What are the symptoms of lymphoma?
- Painless, rubbery LNs
| - B symptoms - pel ebstein fever, weight loss, night sweats, pruritus
85
Why should you ask about contact with cats in a lymphoma history?
Cat scratch fever gives you generalised lymphadenopathy
86
In what cases should enlarged LNs be refered?
6 week history of a node over 1.5cm
OR
6 week history of generalised lymphadenopathy
87
What blood tests should be done in lymphoma and what would they show?
Bloods - FBC, U&E, LFT, ESR (usually normal!!, low Hb and high ESR indicate worse prognosis)
Monospot - EBV is a reactive cause of lymphadenopathy
Viral screen - HIV is associated with lymphoma
Blood film
LDH
88
What is the diagnostic test for lymphoma? What would it show for Hodgkins?
EXCISION NODE/CORE BIOPSY
| - shows Reed Sternburg 'owl cell'
89
What special tests should be done in lymphoma and what do they show?
Genetic sequencing - FISH
PET - increased glycolytic tissue in malig
Bone marrow sampling rarely used as the disease is in the nodes
90
How can lymphoma be classifed?
Grade - Low grade vs High grade
| Histology - Hodgkins vs Non-Hodgkins
91
What is the difference between low grade and high grade?
Low grade - slow growing but incurable, treat if symptomatic
High grade - fast growing but cured with chemotherapy
92
Describe Hodgkins lymphoma
- Reed sternburg cell
- Months-years survival if untreated
- Curable
93
Describe Non-Hodgkins lymphoma
Over 60 types but split into
Indolent - incurable, survival years
Aggressive - chemo, survival months
Very aggressive - chemo, survival weeks
94
Give an example of an indolent, aggressive and very aggressive NHL
Indolent - follicular
Aggressive - DLBCL
Very aggressive - Burkitts
95
How should follicular lymphoma be managed?
Usually stage IV at presentation but only treat if symptomatic with:
- Chlorambucil and steroids
- Rituximab
- Bone marrow transplant
96
Describe the severity of diffuse large B cell lymphoma?
Can develop from CML or follicular
| Severity determined by age, stage, extranodal involvement, performance status and LDH
97
How should DLBCL be treated?
```
R-CHOP
Rituximab
Cyclophosphamide
Hydroxydaunorubicin
Vincristine (oncovin)
Prednisolone
```
98
How is lymphoma staged?
```
Ann Arbour
1 - 1LN
2- >2LN on same side of diaphragm
3 - >2LN on different sides of diaphragm
4 - Disseminated
```
A - no B symptoms
B - weight loss, fever, night sweats
99
What are the complications of lymphoma, and how are the managed briefly?
Tumour lysis syndrome - allopurinol/rasburicase + hydrate
Spinal cord compression - MRI/steroids/surgery
Hypercalcemia - IV bisphosphonates
100
How do patients with bone marrow failure present?
Bruising, fatigue, pallor, organomegaly, SOB, infection
101
Why do patients get organomegaly in anaemia?
Increased demand induces extramedullary haemoatopoiesis in the liver and spleen
102
What do blood tests show in bone marrow failure?
Pancytopenia - bone marrow failure is the leading cause of pancytopenia
103
What can cause pancytopenia?
Increased destruction - sepsis, immune, splenomegaly
| Decreased production - bone marrow failure
104
What investigations should be done in anyone with pancytopenia?
Reticulocyte count, B12/folate, abdo USS, temperature
105
What are the 3 categories of causes of bone marrow failure
1. Aplastic anaemia
2. Megaloblastic anaemia
3. Infiltration of the bone marrow with malignancy
106
What is aplastic anaemia?
A rare stem cell disorder involving pancytopenia and hypoplastic bone marrow, due to drugs (benzene, chemo, gold, suphonamide), congenital or idiopathic
107
How is aplastic anaemia managed?
- Treat underlying cause
- Supportive care - infusions, infection check
- Stem cell transplant from HLA matched sibling
108
What is megaloblastic anaemia?
Production of large, abnormal immature RBCs by the bone marrow, usually due to B12 or folate deficiency.
109
How is megaloblastic anaemia treated? What should you not do?
Give B12/folate replacement (IM)
| DONT give Hb transfusion as the patient has adapted to the anaemia overtime and overload will lead to heart fialure
110
Which blood cancer commonly presents with bone marrow failure. What are the symptoms?
Acute leukemia - sweats, weight loss, flu, anaemia, bleeding etc
111
What is acute leukemia?
Neoplastic disorder of the IMMATURE myeloblasts or lymphoblasts in the bone marrow
112
What investigations should be done in a patient with suspected acute leukemia and what would they show?
Bloods - anaemia, pancytopenia, high number of blasts
Tissue biopsy - huge nuclei
Bone marrow biopsy - blast cells
113
What causes acute leukemia?
- Genetic predisposition - eg. Downs syndrome
- Haematological disease
- Irradiation
- Chemotherapy
114
What are the features of ALL? What important investigation must be done?
```
Affecting lymphocytes (80%B, 20%T), more common in children
BUZZ WORDS - blast cells, parotids/testicles, extra medullar involvement
```
Do lumbar puncture to assess for CNS involvement
115
What are the features of AML? What is the characteristic finding on cytology?
Affecting neutrophils, RBCs, platelets, more common in adults
BUZZ WORDS - downs syndrome, NF1, male, risk of DIC, previous MDS/CML
Auer rods
116
How is acute leukemia managed?
1. Supportive - transfusions, IV fluid, allopurinol
2. Infection - assess risk, start empirical abx
3. Discussion about sperm banking precehmo
4. Chemotherapy + LP if CNS mets suspected (as chemo cant cross BBB_
5. Allogeneic marrow transplant
117
What are the features of CLL?
Often asymptomatic and diagnosed incidentally eg. before an operation
Found in the elderly, no treatment usually required
118
What does a CLL blood film look like?
Lots of small, mature lymphocytes
119
Name 7 conditions that cause thrombosis?
```
Factor V leiden
DVT/PE
Antiphospholipid syndrome
Cerebral sinus thrombosis
Arterial embolus
Metallic heart valves
Ventricular pace maker
```
120
What is factor V leiden?
A point mutation in factor V gene, leading to slow inactivation of Va and hence a tendency to form clots - this is one of the most common causes of inherited procoagulant states
Usually this would be inactivated by protein C
121
What are the RF for thrombosis?
```
Age
Immobilisation
Surgery
Oestrogen
Air travel
Cancer
Antiphospholipid anti bodies
Thrombophilia
```
122
What naturally occurring anticoagulants are deficient in thrombophilia?
Protein C
Protein S
Antithrombin
123
What are the symptoms of a VTE?
DVT - hot unilateral swollen legs
| PE - sudden onset unilateral chest pain
124
What investigations should be done to diagnose a VTE?
DVT - bilateral doppler USS
PE - CTPA
D dimer is helpful in exclusion but has a low specificity so should not be used diagnostically.
125
How should a VTE be managed?
Anticoagulate with LMWH eg. enoxaparin
Anticoagulate with factor Xa inhibitor eg. fonadparinux
Anticoagulate with warfarin
Thrombolysis with alteplase
126
Describe an anticoagulation regimen post VTE using a LMWH
Tinzaparin
| - continue for 5 days or until INR >2 for 2 consecutive readings
127
Describe an anticoagulation regimen post VTE using a factor xa inhibitor
Rivaroxaban
| - continue for 21 days
128
Describe an anticoagulation regimen post VTE using warfarin
Warfarin
- slow onset of action so cover with LMWH during first few days of initiation
- day 1 (5mg)
- day 2 (5mg)
- day 3 (check INR)
- adjust dose accordingly
129
What are the complications of anticoagulation?
| Describe symptoms, and treatment
Anticoagulant associated ICH
- Stroke symptoms within 24-48h of admin
- Treat with beriplex and vitamin K
130
What score is used to predict likelihood of recurrence of VTE?
```
DASH score!!
Positive D dimer - 2
Age < 50 - 1
Male - 1
Female/hormone associated VTE - -1
```
If DASH < = 1, stop anticoagulant
131
What is chronic leukemia?
Neoplastic disease of mature WBCs in the bone marrow, to to progressive accumulation of functionally incompetent WBCs
132
What are the symptoms of chronic leukemia?
Insidious weight loss, fever, sweats, bleeding.
In CLL in particular, it is often an incidental finding
133
What would tests show for CML?
BLOODS - High WCC (neutrophils, basophils, eosinophils) Anaemia
BIOPSY - Philadelphia translocation (9:22) of ABL:BCR
134
How is CML treated?
Tyrosine kinase inhibitors - Imatinib
Hydroxycarbamide
Stem cell transplant
135
What would tests show for CLL?
BLOODS - High lymphocyte count, anaemia
136
How is CLL treated?
```
OFTEN NO TREATMENT
Chemo
Radio
Supportive
Stem cell transplant
```
137
What is the prognosis of chronic leukemia?
CML - chronic, accelerated and blast phase (in which it transforms to AML)
CLL - often never progress, better prognosis
138
What may a blood film of someone with iron deficient anaemia show?
Elliptocytes and hypersegmented neutrophils
139
What would the FBC look like of a patient with anaemia of chronic disease?
Normocytic anaemia
Normal platelets
Increased ferritin
Reduced total iron binding capacity
140
What is the most appropriate measurement of the bodys iron stores?
Serum ferritin
141
What is the most common complication of allogeneic bone marrow transplant?
Graft versus host disease
142
What is the most common complication of allogeneic bone marrow transplant for aplastic anaemia?
Graft failure
143
What is acquired haemophilia?
An autoimmune process in which the body starts making antibodies to factor 8 or 9. Often this is due to an occult malignancy
144
What would blood tests show in a patient with acquired haemophilia?
Grossly elevated APTT
| - no correction with mixed study
145
What are protein C/S deficiencies?
Deficiency of vit K dependent natural anticoagulants - gives a 5 fold increase in VTE risk
146
What is the name of the condition in which patients have urine/serum monoclonal antibodies but do not fulfil the criteria for multiple myeloma?
Monoclonal gammopathy of uncertain significance
- 2% risk of transforming into MM
