Haematology Flashcards
(122 cards)
1
Q
describe the subunits of fetal and adult Hb
A
Fetal = 2 alpha and 2 gamma subunits
Adult = 2alpha and 2 beta subunits
2
Q
difference between adult Hb and fetal Hb
A
Fetal has a greater affinity to oxygen than adult Hb. Oxygen binds to fetal Hb and is more reluctant to let go= steal oxygen away from the mother’s Hb when nearby in the placenta. If the fetal and maternal HB had the same affinity for oxygen, there would be no incentive for the oxygen to switch from the maternal blood to fetal blood.
3
Q
what happens to fetal Hb at birth
A
From 32 to 36 weeks gestation, production of HbF decreased. At the same time HbA is produced in greater quantities. gradual transfer HbF to HbA. At birth, around half the Hb produced is HbF and half is HbA. By 6 months of age, very little fetal Hb produced. Eventually, RBC contain entirely HbA.
4
Q
what is the significance of fetal Hb in Sickle Cell Disease?
A
In sickle cell disease, a genetic abnormality coding for Beta subunit is responsible for causing the sickle shape of RBC. Fetal Hb does not lead to sickling of RBC because there is no Beta Subunit in the structure.
5
Q
what is Hydroxycarbamide?
A
Hydroxycarbamide can be used to increase the production of fetal Hb in sickle cell. This has protective effect against sickle cell crises and acute chest syndrome
6
Q
what are some causes for anaemia in infancy?
A
Physiological anaemia of infancy causes most cases in infancy Others:
- Anaemia of prematurity
- Blood loss
- Haemolysis
- Twin-twin transfusion syndrome
Haemolysis is a common cause of anaemia in infancy. No causes in neonate:
- Haemolytic disease of the newborn
- Hereditary spherocytosis
- G6PD deficiency
7
Q
normal hb values
A
8
Q
what is physiological anaemia of infancy?
A
Normal dip Hb six to nine weeks of age in healthy term babies. High oxygen delivery to tissues caused by the high Hb levels at birth cause negative feedback. Production of EPO in the kidneys is suppressed and subsequently there is a reduction in Hb by the bone marrow. High oxygen results in lower Hb production
9
Q
what is anaemia of prematurity?
A
Premature neonates are much more likely to become significantly anaemic during the first few weeks of life compared with term infants. More premature= more likely to require 1 or more transfusions for anaemia. More likely if unwell at birth.
Premature neonates become anaemic for a number of reasons
- Less time utero for iron from mother
- RBC creation cannot keep up with the rapid growth in the first few weeks
- Reduced EPO levels
- Blood tests remove significant proportion of their circulating volume
10
Q
what is haemolytic disease of the newborn? and what test is relevant?
A
Where anti d antibodies from the mother cross placenta and if baby is rhesus positive, antibodies attack to fetal RBC and trigger fetal immune system to attack own RBC = haemolysis = anaemia = high bilirubin levels
Direct Coombs test – check for immune haemolytic anaemia - +ve in HDN
11
Q
what are some causes for anaemia in older children?
A
- Iron def anaemia secondary to dietary insufficiency- MOST COMMON
- Blood loss- menstruation
RARER INCLUDE:
- Sickle cell anaemia
- Leukaemia
- Hereditary spherocytosis
- Hereditary eliptocytosis
- Sideroblastic anaemia
(Worldwide a common cause of blood loss causing chronic anaemia and iron deficiency is helminth infection, with roundworms, hookworms or whipworms. Common in developing countries & those living in poverty, unusual in the UK. Treatment= single dose albendazole or mebendazole.)
12
Q
how to we categorise anaemia?
(3 categories)
A
microcytic
macrocytic
normocytic
13
Q
what does microcytic mean and what are some causes?
A
low MCV = small RBC
TAILS - thalassaemia, anaemia of chronic disease, iron deficiency, lead poisoning, sideroblastic anaemia
14
Q
what does macrocytic mean and what are some causes?
A
large MCV = large RBC
magaloblastic = impaired DNA synthesis (B12/folate deficiency)
normoblastic - alcohol, reticulocytosis, hypothyroidism, liver disease, azathioprine
15
Q
what does normocytic mean and what are some causes?
A
normal MCV = normal RBC
- 3A (Acute blood loss, Anaemia chronic disease, Aplastic anaemia)
- 2H (Haemolytic anaemia, Hypothyroidism)
16
Q
what are some symptoms of anaemia?
A
- Tiredness
- SOB
- Headaches
- Dizziness
- Palpitations
- Worsening other conditions
17
Q
what are some signs and symptoms specific to iron deficiency anaemia?
A
pica - dietary cravings for things like dirt
hair loss
signs - koilonychia, angular chelitis, atrophic glossitis, brittle hair and nails
18
Q
what are some signs of anaemia?
A
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised RR
19
Q
what investigations are done for anaemia?
A
- FBC for Hb and MCV
- Blood film
- Reticulocyte count
- Ferritin (low iron deficiency)
- B12 and folate
- Bilirubin (raised in haemolysis)
- Direct Coombs test (autoimmune haemolytic anaemia)
- Hb electrophoresis (haemaglobinopathies)
- Reticulocytes (high in blood loss or haemolysis as active production to replace lost cells)
20
Q
how is anaemia managed?
A
Depends underlying cause. Severe require blood transfusions.
Iron=iron supplementation.
21
Q
what are the 3 broad causes of iron deficiency anaemia?
A
dietary insufficiency - most common
loss of iron
inadequate absorption
22
Q
where in the gut is iron absorbed?
A
Iron absorbed in the duodenum and jejunum. Requires the acid in the stomach to keep the iron in soluble ferrous (Fe2+) form. Less acid in the stomach = changes to insoluble Ferric 3+ Meds such as PPI can interfere with iron absorption. Crohns or coeliac also affect the duodenum and jejunum- reduced absorption.
23
Q
what does iron travel as in the blood and on what?
A
Iron travels in blood as ferric ions (FE3+) on transferrin
24
Q
what is ferritin and what is its significance?
A
form iron takes when deposited and stored in cells
released from cells in inflammation such as infection or cancer.
- Low = highly suggestive or iron deficiency anaemia
- High= hard to interpret as inflammation or overload.
- Normal ferritin can have iron def anaemia, particularly if they have reasons to have raised such as inflammation.
25
what is transferrin saturation?
indication of total iron in body
26
how is iron deficiency anaemia managed?
Treating underlying cause and correcting anaemia. In children the underlying cause is usually dietary deficient, so dietician input important.
Can supplement with ferrous sulphate or fumarate. This slowly correct iron deficiency. Oral iron causes constipation and black coloured stools. Unsuitable if malabsorption the cause of anaemia.
Blood transfusions are rarely necessary. Children generally able to tolerate a low Hb well and can be given time to correct their anaemia.
27
what is leukaemia?
Cancer of a particular line of stem cells in the bone marrow. Causes unregulated production of certain typed of blood cells. Types of leukaemia can be classified depending on how regularly they progress (chronic slow and acute is fast) and the cell line that is affected (myeloid- Granulocytes, monocytes, macrophages, and dendritic cells (DCs) or Lymphoid)
28
what are the 3 types of leukaemia? which is most common?
* **Acute lymphoblastic Leukaemia** (ALL) most common in children
* **Acute Myeloid Leukaemia** (AML) is the next most common
* **Chronic Myeloid Leukaemia** RARE
29
what age groups are ALL and AML common in?
* ALL peaks 2-3yrs
* AML peaks aged under 2 years
30
what is the pathophysiology of leukaemia?
A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white cell. The excessive production of one cell can lead to suppression of the other cell lines, causing underproduction of the other cell types= **Pancytopenia** which is a combination of low:
* RBC (anaemia)
* WBC (leukopenia)
* Platelets (thrombocytopenia)
31
what is pancytopenia?
**Pancytopenia** which is a combination of low:
* RBC (anaemia)
* WBC (leukopenia)
* Platelets (thrombocytopenia)
32
what are some risk factors for leukaemia?
* radiation exposure (main risk)
* Down’s syndrome
* Klinefelter syndrome
* Noonan syndrome
* Fanconi’s anaemia
33
how does leukaemia present?
* Persistent fatigue
* Unexplained fever
* Failure to thrive
* Weight loss
* Night sweats
* Pallor
* Petechiae (abnormal bruising from thrombocytopenia)
* Unexplained bleeding- thrombocytopenia
* Abdo pain
* Generalised lymphadenopathy
* Unexplained or persistent bone or joint pain
* Hepatosplenomegaly
34
how is leukaemia diagnosed?
Refer unexplained petechiae or hepatomegaly for immediate specialist assessment – NICE reccomendation
Urgent FBC w/in 48Hr
To establish diagnosis:
* FBC- anaemia, leukopenia, thrombocytopenia, and high no of abnormal WBC
* Blood film- blast cells- precursors to circulating cells
* Bone marrow biopsy
* Lymph node biopsy
Further for staging:
* CXR
* CT scan
* LP
* Genetic analysis and immunophenotyping of the abnormal cells
35
how is leukaemia managed?
Paediatric oncology MDT
Primarily treated w/ chemotherapy
Others:
* Radiotherapy
* Bone marrow transplant
* Surgery
36
what are some complications of leukaemia?
* Failure to treat the leukaemia
* Stunted growth and development
* Immunodeficiency and infections
* Neurotoxicity
* Infertility
* Secondary malignancy
* Cardiotoxicity
37
what is the prognosis for leukaemia?
Overall cure rate for ALL is around 80%, but prognosis depends on individual factors. Outcomes less positive AML
38
what is immune thrombocytopenia?
a condition characterised by idiopathic thrombocytopenia causing a purpuric rash.
39
what is the pathophysiology of immune thrombocytopenic purpura and what type of hypersensitivity reaction is it?
type 2 hypersensitivity reaction
Caused by production of antibodies that target and destroy platelets. This can happen spontaneously, or it can be triggered by something, such as viral infection.
40
how does immune thrombocytopenic purpura present?
Usually present U10yo. Often there is a hx of a recent viral illness. Onset over 24-48Hrs:
* Bleeding
* Bruising
* Petechial or purpuric rash- bleeding under the skin
41
what are petechiae, purpuras and eccymoses?
* **Petechiae**- pin-prick spots (around 1mm) bleeding under the skin.
* **Purpuras** are larger (3-10mm) spots of bleeding under skin.
* **Ecchymoses** (\>10mm)
they are all non-blanching
42
how is immune thrombocytopenic purpura managed?
Urgent FBC for the platelet count
Other values on the FBC should be normal/ Other causes should be exclude - Heparin induced thrombocytopenia and leukaemia
Severity management depends how far the platelet count falls. Usually no treatment required as platelets return to usual. Around 70% remit spontaneously in 3/12
Treatment may be required if pt is actively bleeding or severe thrombocytopenia (platelets below 10)
* Prednisolone
* IVIg
* Blood transfusions if required
* Platelet transfusions only work temporarily as ab will destroy again
* Splenectomy
Key education and advice is necessary:
* Avoid contact sports
* Avoid IM injections and procedures such as LP
* Avoid NSAIDs, aspirin and blood thinning medications
* Advice on managing nosebleeds
* Seek help after any injury that may cause internal bleeding- eg car accidents or head injuries
43
what are the complications of ITP?
* Chronic ITP
* Anaemia
* Intracranial and subarachnoid haemorrhage
* GI bleeding
44
what is sickle cell anaemia?
genetic condition that causes sickle shaped RBC which are more easily destroyed leading to haemolytic anaemia
45
what is the abnormal variant of Hb in sickle cell anaemia?
HbS
46
what is the inheritance of sickle cell?
**Autosomal recessive** where there is an abnormal gene for beta-globin on chromosome 11.
One copy of the gene results in sickle-cell trait - usually asymptotic but 2=disease.
47
what is the significance of sickle cell in malaria?
More common in areas of Malaria= Africa, India, the Middle East and the Caribbean. Having 1 copy reduces severity of Malaria. As a result= selective advantage.
48
how is sickle cell diagnosed?
Pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy.
Sickle cell disease is also tested for on the ***newborn screening heel prick test*** at 5 days of age.
49
what are some complications of sickle cell?
* Anaemia
* Increased risk of infections
* Stroke
* Avascular necrosis of large joints such as hip
* Pulmonary HTN
* Painful and persistent penile erection (priapism)
* CKD
* Sickle cell crises
* Acute chest syndrome
* HF, Cardiomegaly, renal dysfunct, leg ulcers, psych problems
50
what is the general management of sickle cell?
* Avoid dehydration and other triggers of crises
* Ensure vaccines are up to date
* Antibiotic prophylaxis to protect against infection- Penicillin V
* Hydroxycarbamide can be used to stimulate production of fetal Hb- protective against crises
* Blood transfusion for severe anaemia
* Bone marrow transplant can be curative
51
what is a sickle cell crisis and how are they managed?
umbrella term for spectrum of acute crises related to the condition. Range from mild to life threatening. Can occur spontaneously or be triggered by stresses such as, infection, dehydration or significant life events.
non specific treatment for crisis - supportive mx
* Low threshold for admission to hospital
* Treat any infection
* Keep warm
* Keep well hydrated IVF
* Simple analgesia such as paracetamol and ibuprofen (Avoid renal impairment)
* Penile aspiration for priapism
52
what are the 4 sickle cell crisis?
1. **Vaso-occlussive Crisis (AKA Painful crisis)**
2. **Splenic Sequestration Crisis**
3. **Aplastic Crisis**
4. **Acute Chest Syndrome**
53
what is a vaso-occlussive crisis?
Clogs capillaries and causing distil ischaemia. Dehydration and raised haematocrit.
symtoms = pain, fever, those of triggering infection, priapism in man
54
what is a splenic sequestration crisis
caused by red blood cells blocking blood flow within the ***spleen***
acutely enlarged and painful spleen, pooling of blood in the spleen can lead to severe anaemia and circulatory collapse
supportive mx with blood transfusions, fluid resus and treat anaemia and shock
splenectomy prevents further crisis and often done is recurrent cases as can lead to splenic infarction = increased infection risk
55
what is an aplastic crisis?
temporary loss of creation of new blood cells - triggered by parvovirus b19
= significant aneamia
supportive with blood transfusions if necessary - usually resolves within 1 week
56
what is acute chest syndrome
diagnosis requires fever or resp symptoms with infiltrates seen on on CXR
due to infection or non infective causes like pulmonary vaso-occlusion or fat emboli
medical emergency with high mortality
supportive mx and treat underlying cause:
* ABX or antivirals for infections
* Blood transfusions for anaemia
* Incentive spirometry using a machine that encourages effective and deep breathing
* Artificial ventilation with NIV or intubation may be required
57
what is thalassaemia?
genetic defect in the protein chains that make up Hb
* Hb has 2 alpha chains and 2 beta chains - Defect in alpha = alpha thalassaemia, defect in beta = beta thalassaemia - both conditions are **autosomal recessive**.
58
thalassaemia cont.
* RBC are more fragile and breakdown more readily.
* Spleen acts as a sieve to filter the blood and remove older blood cells.
* Collects all destroyed cells = splenomegaly.
* Bone Marrow expands to produce extra RBC to compensate for chronic anaemia = more susceptible to fractures and prominent features, such as a pronounced forehead and malar eminences (cheek bones).
59
what are some signs and symptoms of thalassaemia?
* Microcytic anaemia (low mean corpuscular volume)
* Fatigue
* Pallor
* Jaundice
* Gallstones
* Splenomegaly
* Poor growth and development
* Pronounced forehead and malar eminences
60
how can Thalassaemia be diagnosed?
* FBC – shows microcytic
* Hb electrophoresis is used to diagnose globin abnormalities
* DNA testing can be used to look for genetic abnormality
* Pregnant women in the UK are offered a screening test
61
what is iron overload in thalassaemia?
Occurs in thalassaemia bc of the faulty creation of RBC, recurrent transfusions, and increased absorption of iron in the gut in response to anaemia.
Pt have serum ferritin levels checked
62
what are the features of iron overload?
* fatigue
* liver cirrhosis
* infertility
* impotence
* heart failure
* arthritis
* diabetes
* Osteoporosis and joint pain
63
how is iron overload in thalassaemia managed?
limiting transfusions and performing iron chelation
64
what is alpha thalassaemia and how is it managed?
defect in the alpha chains which is coded for on chromosome 16
**managed** with FBC monitoring, blood transfusions, splenectomy, bone marrow transplant can be curative
65
what is beta thalassaemia?
defect in the beta chains on chromosome 11
abnormal copies retain some function
deletion leads to no function
3 types
66
what are the 3 types of beta thalassaemia and how are they managed??
**3. Thalassaemia Minor =** Carriers= one normal gene and one abnormal gene .
Mild microcytic anaemia-monitor and no active treatment
**2. Thalassaemia Intermedia**
Two abnormal copies - 2 defective or one defective and one deletion.
More significant microcytic anaemia.
Monitor and occasional blood transfusions. May require more- may require iron chelation to prevent iron overload.
**3. Thalassaemia Major**
Homozygous for the deletion genes. They have no functioning beta globin genes at all. No funct at all. This is the most severe form and usually presents with SEVERE ANAEMIA AND FAIL TO THRIVE IN EARLY CHILDHOOD
**Thalassaemia major sauses:**
* Severe microcytic anaemia
* Splenomegaly
* Bone deformities
Manage= regular blood transfusion, iron chelation and splenectomy. Bone marrow transplant can potentially be curative.
67
what is hereditary speherocytosis?
RBC are sphere shaped, making fragile and easily destroyed when passing through the spleen
autosomal dominant
68
how does hereditary spherocytosis present?
* Jaundice
* Anaemia
* Gallstones
* Splenomegaly
* episodes of haemolytic crisis often triggered by infection where heamolysis, anaemia and jaundice are more significant
* can develop aplastic crisis - increased anaemia, haemolysis, jaundice, without normal response from bone marrow creating new RBC (normally bone marrow responds to haemolysis by producing RBC faster = extra reticulocytes
* aplastic - no response and triggered by parvovirus
69
how is hereditary spherocytosis managed?
diagnosed by FH and clinical features along with spherocytes on blood film
mean corpuscular hb conc raised on fbc
reticulocytes will be raised due to rapid turnover of RBC
70
how is hereditary spherocytosis managed?
* Folate supplementation and splenectomy.
* Removal of the gall bladder may be required if gallstones are a problem.
* Transfusions may be required during acute crises.
71
what is hereditary elliptocytosis?
* Very similar to hereditary spherocytosis except the RBC are ellipse shaped.
* Also **autosomal dominant**.
* Presentation and management are very similar.
72
what is G6PD deficiency?
G6PD deficiency is a condition where there is a defect in the *G6PD enzyme* normally found in all cells in the body.
73
what is the inheritance of G6PD deficiency
***X linked recessive*** pattern, meaning it usually affects males, as they have only a single copy of the gene on their single X chromosome
more common in Mediterranean, middle eastern and African patients
74
what is significant about the triggers in G6PD deficiency?
causes crisis that are triggered by infections, mediations and broad beans
***look out for a patient that becomes jaundice and anaemic after eating broad beans, developing an infection or being treated with antimalarial medications. The underlying diagnosis might be G6PD deficiency.***
75
what is the pathophysiology of G6PD deficiency?
G6PD enzyme is responsible for helping protect cells from damage by reactive oxygen species (ROS)
ROS are reactive molecules that contain o2 produced by normal cell metabolism and in high quantities during stress on the cell
particularly important in RBC as deficiency in G6PD makes cells more vulnerable to ROS leading to haemolysis
Periods of increased stress, with a higher production of ROS, can lead to ***acute haemolytic anaemia***
76
how does G6PD present?
neonatal janudice
anaemia, intermittent jaundice in response to triggers, gallstones, splenomegaly
77
what will be seen on blood film of G6PD deficiency?
***Heinz bodies*** may be seen on a on ***blood film***. Heinz bodies are blobs of ***denatured haemoglobin*** (“***inclusions***”) seen within the ***red blood cells***.
78
how can G6PD deficiency be diagnosed?
doing a G6PD enzyme assay
79
how is G6PD deficiency managed?
avoid triggers - avoiding fava beans and certain medications
80
what are some medications which should be avoided in G6PD deficiency?
* Primaquine (an antimalarial)
* Ciprofloxacin
* Nitrofurantoin
* Trimethoprim
* Sulfonylureas (e.g gliclazide)
* Sulfasalazine and other sulphonamide drugs
81
what is lymphoma?
cancer in the lymphatic system
cancerous cells proliferate within the lymph nodes and cause lymph nodes to become abnormally large = lymphadenopathy
82
what are the 2 main categories of lymphoma?
hodgkins lymphoma - specific disease
non-hodgkin's lymphoma - encompasses all other lymphomas
83
what is hodgkin's lymphoma?
proliferation of lymphocytes
bimodal age distribution - peaks of 20 and 75
84
what are some risk factors for lymphoma?
HIV
EBV
Autoimmune conditions like RA and sarcoidosis
FHx
85
how does hodgkin's lymphoma present? key symptom, B symptoms + others
_key symptom_ = **lymphadenopathy** - neck, axilla, inguinal
non-tender and feel rubbery
some patients will experience pain in lymph nodes when they drink alcohol
_B symptoms_ = fever, weight loss, nigh sweats
_others_ = fatigue, itching, cough, SOB, abdo pain, recurrent infections
86
what investigations are done for hodgkins lymphoma?
**lactate dehydrogenase** - often raised in HL - non specific
**lymph node biopsy** - key diagnostic test - Reed-Sternberg cell
**CT, MRI, PET** - dx and staging and other tumours
87
what is a Reed-Sternberg cell?
Key finding from lymph node biopsy in patients with Hodgkin’s lymphoma.
They are ***abnormally large B cells*** that have ***multiple nuclei*** that have ***nucleoli*** inside them.
appearance of face of owl with large eyes
88
what is Ann Arbor Staging?
used for both NHL and HL
important to note whether the affected nodes are above or below the diaphragm
* Stage 1: Confined to one region of lymph nodes.
* Stage 2: In more than one region but on the same side of the diaphragm (either above or below).
* Stage 3: Affects lymph nodes both above and below the diaphragm.
* Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.
89
how is hodgkins lymphoma managed?
chemo and radiotherapy
aim to cure
usually successful but risk of relapse, other haematological cancers and side effects
chemo = risk of leukaemia and infertility
radiotherapy = risk of cancer, damage to tissue and hypothyroidism
90
what is non-hodgkin lymphoma?
group of lymphomas. There are almost endless types of lymphoma. A few notable ones are:
* ***Burkitt lymphoma*** is associated with Epstein-Barr virus, malaria and HIV.
* ***MALT lymphoma*** affects the ***mucosa-associated lymphoid tissue***, usually around the ***stomach***. It is associated with ***H. pylori*** infection.
* ***Diffuse large B cell lymphoma*** often presents as a rapidly growing painless mass in patients over 65 years.
91
risk factors for non-hodgkin lymphoma
* HIV
* Epstein-Barr Virus
* H. pylori (MALT lymphoma)
* Hepatitis B or C infection
* Exposure to pesticides and a specific chemical called ***trichloroethylene*** used in several industrial processes
* Family history
92
how does NHL present?
similar to HL and often differentiated when lymph node biopsy is done
93
how is NHL managed?
* Watchful waiting
* Chemotherapy
* Monoclonal antibodies such as ***rituximab***
* Radiotherapy
* Stem cell transplantation
94
what is Haemophilia and what causes the 2 types, A&B?
inherited severe bleeding disorders
X linked recessive - almost exclusively affects males
A is deficiency in factor VIII
B is deficiency in factor IX (aka Christmas disease)
95
what are some signs and symptoms of haemophilia?
Excessively bleeding in response to minor trauma and also at risk of spontaneous haemorrhage without any trauma
intracranial haemorrhage, haematomas, cord bleeding in neonates
Spontaneous bleeding into joints and muscles
96
what are some sites of abnormal bleeding in haemophilia?
* Gums
* Gastrointestinal tract
* Urinary tract causing haematuria
* Retroperitoneal space
* Intracranial
* Following procedures
97
how is haemophilia diagnosed?
based on ***bleeding scores***, ***coagulation factor assays*** and ***genetic testing***
98
how is haemophilia managed?
specialist mx
affected clotting factors can be replaced by IV infusions - prophylactically or in response to bleeding (complication = antibody formation against clotting factors resulting in treatment becoming ineffective)
99
Acute episodes of bleeding or prevention of excessive bleeding during surgical procedures involves what?
* ***Infusions*** of the affected factor (VIII or IX)
* ***Desmopressin*** to stimulate the release of ***von Willebrand Factor***
* ***Antifibrinolytics*** such as ***tranexamic acid***
100
what is von willebrand disease and what causes it?
most common inherited cause of abnormal bleeding
autosomal dominant
causes involve deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factors - 3 types 1-3 with 3 being the most severe
101
how does von willebrand disease present?
history of unusually easy, prolonged or heavy bleeding:
* Bleeding gums with brushing
* Nose bleeds (***epistaxis***)
* Heavy menstrual bleeding (***menorrhagia***)
* Heavy bleeding during surgical operations
102
how is von willebrand disease diagnosed?
based on history of abnromal bleeding
FHx v important
bleeding assessment tools and laboratory investigations
hard to dx due to lots of underlying causes - beyond scope of exams!
103
how is von willebrand disease managed? including mangement in women with heavy bleeding during menstruation?
does not require day to day treatment. Management needed in response to major bleeding/trauma or in preparation for operations to prevent bleeding
* ***Desmopressin*** can be used to stimulates the release of VWF
* ***VWF*** can be infused
* ***Factor VIII*** is often infused along with plasma-derived VWF
Women with VWD that suffer from heavy periods can be managed by a combination of:
* Tranexamic acid
* Mefanamic acid
* Norethisterone
* Combined oral contraceptive pill
* Mirena coil
* ***Hysterectomy*** may be required in severe cases.
104
what is pancytopenia?
reduction in RBC, WBC, platelets
105
what are some common causes of pancytopenia?
* Aplastic anaemia
* Acute leukaemia
* Hypersplenism
* Severe megaloblastic anaemia
* Sepsis
* Malaria
* SLE
106
what are some clinical features of pancytopenia?
* Fatigue
* Easy bruising
* Pallor
* Tachycardia
* Tachypnoea
* Epistaxis
* Recurrent infections
107
how is pancytopenia managed?
* Watchful monitoring (mild cases)
* Immunosuppressant drugs
* Bone marrow transplant
* Blood transfusions
* Stem cell transplant
108
what is disseminated intravascular coagulopathy?
Inappropriate activation of the clotting cascades, resulting in thrombus formation and depletion of clotting factors and platelets.
IL1 and TNF cause up regulation of clotting cascade.
109
what are the clinical features of DIC?
* Bleeding- epistaxis, gingival, haematuria, bleed cannula sites.
* Fever
* Confusion
* Coma
* Often in context of severe systemic disease
Signs= Petechiae, bruising, confusion and hypotension
110
What causes DIC?
* Sepsis
* Major burns
* Shock
* Malignancy (e.g. leukaemia)
* Liver disease (e.g. Reye’s syndrome)
* Respiratory distress syndrome
111
what are some risk factors for DIC?
Major trauma and burns, multiple organ failure, severe sepsis or infection, severe obstetric complications, solid tumours or haematological malignancies
112
what are some investigation finding for DIC?
* Thrombocytopenia
* Increased PT
* Increased D-Dimers
* Decreased Fibrinogen
* Schistocytes
* High fibrin degradation products
113
how is DIC managed?
* Replacement therapy
* Anticoagulation
* Heparin
114
what are some causes of hyposplenism?
* splenectomy
* sickle-cell
* coeliac disease, dermatitis herpetiformis
* Graves' disease
* systemic lupus erythematosus
* amyloid
115
what infections are patients particularly at risk from following splenectomy?
pneumococcus, haemophilus, meningococcus capnocytophaga canimorus
116
describe the vaccinations given in hyposplenism
* if elective, should be done 2 weeks prior to operation
* Hib, meningitis A & C
* annual influenza vaccination
* pneumococcal vaccine every 5 years
117
what antibiotic prophylaxis are patients given?
penicillin V: It is generally accepted though that penicillin should be continued for at least 2 years and at least until the patient is 16 years of age, although the majority of patients are usually put on antibiotic prophylaxis for life
118
what are some indications for splenectomy?
* Trauma: 1/4 are iatrogenic
* Spontaneous rupture: EBV
* Hypersplenism: hereditary spherocytosis or elliptocytosis etc
* Malignancy: lymphoma or leukaemia
* Splenic cysts, hydatid cysts, splenic abscesses
119
how does an elective splenectomy differ from that of an emergency splenectomy?
spleen is often huge in elective and needs to be macerated inside a specimen bag to facilitate extraction during laparoscopic surgery
120
what are some complications of splenectomy?
* Haemorrhage (may be early and either from short gastrics or splenic hilar vessels
* Pancreatic fistula (from iatrogenic damage to pancreatic tail)
* Thrombocytosis: prophylactic aspirin
* Encapsulated bacteria infection e.g. *Strep. pneumoniae*, *Haemophilus influenzae* and *Neisseria meningitidis*
121
what changes are seen post splenectomy?
* Platelets will rise first (therefore in ITP should be given after splenic artery clamped)
* Blood film will change over following weeks, Howell-Jolly bodies will appear
* Other blood film changes include target cells and Pappenheimer bodies
* Increased risk of post-splenectomy sepsis, therefore prophylactic antibiotics and pneumococcal vaccine should be given.
122
what causes post splenectomy sepsis?
* Typically occurs with encapsulated organisms
* Opsonisation occurs but then not recognised
