Chapter Six Haematology
MAP 6.3 Bleeding Disorders
Map 6.3 Bleeding Disorders
Haematology
99
BERNARD–SOULIER SYNDROME What is Bernard–Soulier syndrome?
This is an autosomal recessive bleeding disorder.
Causes
This is a hereditary condition that leads to deficiency of glycoprotein (Gp) Ib.
Investigations
•
- Bleeding time, normal or ¯ platelet count.Treatment
•
Conservative: patient education.•
Medical:○ Desmopressin may decrease bleeding time.
○ Recombinant activated factor VII.
CLOT FORMATION
This consists of 4 steps. Defects in steps 2–4 may lead to a bleeding disorder.
1 Vessel constriction.
2 Platelet adhesion and aggregation: Glanzmann’s thrombasthenia, von Willebrand disease, Bernard–Soulier syndrome.
3 Blood coagulation: haemophilia. 4 Fibrinolysis: antiplasmin deficiency.
HAEMOPHILIA What is haemophilia?
This is an inherited condition that impairs the body’s ability to coagulate the blood.
Causes
This is a hereditary condition. There are two forms of haemophilia:
•
Type A: lack of factor VIII.•
Type B: lack of factor IX.Investigations
•
Normal prothrombin time, - partial thromboplastin time.Treatment
•
Conservative: patient education. Avoid aspirin, NSAIDs, heparin and warfarin.•
Medical: replace deficient clotting factor with regular infusions.GLANZMANN’S THROMBASTHENIA What is Glanzmann’s thrombasthenia?
This is a rare autosomal recessive or acquired autoimmune condition in which platelets are deficient of GpIIb/IIIa. GpIIb/IIIa binds fibrinogen.
Causes
Disease of hereditary or acquired autoimmune cause.
Investigations
•
- Bleeding time.Treatment
•
Conservative: patient education. Avoid aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs).•
Medical:○ Desmopressin.
○ Recombinant activated factor VII.
VON WILLEBRAND DISEASE What is von Willebrand disease?
This is the most common hereditary coagulation disorder, which involves a defect in von Willebrand factor (VWF). The function of von Willebrand factor is to bind GpIb receptor on platelets to subendothelial collagen.
Causes
Hereditary condition. There are many different types of von Willebrand disease, but the most common are type 1, type 2, type 3 and type Normandy.
Investigations
•
- Activated partial thromboplastin time, - Bleeding time, normal prothrombin time, ¯ VWF antigen, ¯ factor VIIIc.Treatment
•
Conservative: patient education. Avoid aspirin and NSAIDs.•
Medical: desmopressin may be useful, but is not helpful in type 3 von Willebrand disease.VITAMIN K INSUFFICIENCY What is vitamin K insuffiency?
This avitaminosis occurs when there is decreased vitamin K1 or vitamin K2 or both. This results in:
•
¯ Synthesis of factors II, VII, IX and X.•
¯ Synthesis of proteins C and S.Causes
•
Drugs, e.g. warfarin.•
Malnutrition.•
Malabsorption.•
Alcoholism.•
Cystic fibrosis.•
Chronic kidney injury.•
Cholestatic disease.Investigations
•
- Prothrombin time, normal or - partial thromboplastin time.Treatment
•
Conservative – patient education. Dietary advice about food rich in vitamin K•
Medical – treat cause. Vitamin K supplements.MAP 6.3 Bleeding Disorders
Map 6.3 Bleeding Disorders
Chapter_06.indd 99
Haematology
100 Map 6.4 Leukaemia
Causes
Neoplasm Cause
ALL Possibly a genetic susceptibility coupled with an environmental trigger
Exact cause unknown
Comment
Commonest cancer in children Often spreads to central nervous system Associations – DIP:
•
Down’s syndrome•
Ionising radiation•
PregnancyUsually affects adults over 60 years old Affects B lymphocytes
Positive ZAP-70 marker is associated with a worse prognosis
CLL
AML Exact cause unknown Risk factors include:
•
Myeloproliferative disease•
Alkylating agents•
Ionising radiation exposure•
Down’s syndromeCommonest leukaemia in adults Rapidly progressing
Auer rods on microscopy are diagnostic
CML Exact cause unknown Risk factor: ionising radiation exposure
Usually affects males 40–60 years old 80% associated with the Philadelphia chromosome t[9;22], forming bcr-abl fusion gene
AML Bone marrow failure Malaise
Weight loss Night sweats CML Bone marrow failure
Hepatosplenomegaly Malaise
Weight loss Night sweats
Signs and symptoms
Neoplasm Clinical features
ALL Bone marrow failure Bruising Shortness of breath Purpura Malaise Weight loss Night sweats Asymptomatic Bone marrow failure Nontender lymphadenopathy Hepatosplenomegaly Malaise Weight loss Night sweats CLL What is leukaemia?
This is a rare neoplasm of the blood or bone marrow. It is classified into lymphoid and myeloid neoplasms that may present chronically or acutely. These 4 classifications are:
1 Acute lymphoblastic leukaemia (ALL). 2 Chronic lymphocytic leukaemia (CLL). 3 Acute myeloid leukaemia (AML). 4 Chronic myeloid leukaemia (CML).
Treatment Treatment ALL Conservative CLL Chlorambucil Fludarabine Rituximab Prednisolone Cyclophosphamide Patient education; refer to Macmillan nurses
Medical Induce remission and maintenance To induce remission:
•
Dexamethasone•
Vincristine•
Anthracycline antibiotics•
Cyclophosphamide Maintenance:•
Methotrexate•
Mercaptopurine•
Cytarabine•
Hydrocortisone AML Patients <60 years:chemotherapy with an anthracycline and cytarabine or methotrexate
Patients >60 years:
palliative anthracycline, cytarabine or mitoxantrone
If M3 type AML, i.e. acute promyelocytic leukaemia (APML), then add all-trans retinoic acid to the therapeutic regime
CML
Imatinib
Patients <60 years may be considered for allogeneic stem cell transplantation Other treatments include alpha-interferon, vincristine, prednisolone, cytarabine and daunorubicin Investigations
•
Bloods: FBC, WCC, platelets, U&Es, LFTs, ESR, CRP.•
Bone marrow biopsy, lymph node biopsy.•
Radiology: X-ray, ultrasound scan, CT scan, MRI.•
AML and ALL are classified using the French–American–British (FAB) classification.Complications
•
Death.•
Increased risk of infection.•
Haemorrhage: pulmonary, intracranial.•
Depression.•
Complication of chemotherapy. MAP 6.4 Leukaemia 08/12/14 6:16 PMHaematology
101 Map 6.4 Leukaemia
Causes
Neoplasm Cause
ALL Possibly a genetic susceptibility coupled with an environmental trigger
Exact cause unknown
Comment
Commonest cancer in children Often spreads to central nervous system Associations – DIP:
•
Down’s syndrome•
Ionising radiation•
PregnancyUsually affects adults over 60 years old Affects B lymphocytes
Positive ZAP-70 marker is associated with a worse prognosis
CLL
AML Exact cause unknown Risk factors include:
•
Myeloproliferative disease•
Alkylating agents•
Ionising radiation exposure•
Down’s syndromeCommonest leukaemia in adults Rapidly progressing
Auer rods on microscopy are diagnostic
CML Exact cause unknown Risk factor: ionising radiation exposure
Usually affects males 40–60 years old 80% associated with the Philadelphia chromosome t[9;22], forming bcr-abl fusion gene
AML Bone marrow failure Malaise
Weight loss Night sweats CML Bone marrow failure
Hepatosplenomegaly Malaise
Weight loss Night sweats
Signs and symptoms
Neoplasm Clinical features
ALL Bone marrow failure Bruising Shortness of breath Purpura Malaise Weight loss Night sweats Asymptomatic Bone marrow failure Nontender lymphadenopathy Hepatosplenomegaly Malaise Weight loss Night sweats CLL What is leukaemia?
This is a rare neoplasm of the blood or bone marrow. It is classified into lymphoid and myeloid neoplasms that may present chronically or acutely. These 4 classifications are:
1 Acute lymphoblastic leukaemia (ALL). 2 Chronic lymphocytic leukaemia (CLL). 3 Acute myeloid leukaemia (AML). 4 Chronic myeloid leukaemia (CML).
Treatment Treatment ALL Conservative CLL Chlorambucil Fludarabine Rituximab Prednisolone Cyclophosphamide Patient education; refer to Macmillan nurses
Medical Induce remission and maintenance To induce remission:
•
Dexamethasone•
Vincristine•
Anthracycline antibiotics•
Cyclophosphamide Maintenance:•
Methotrexate•
Mercaptopurine•
Cytarabine•
Hydrocortisone AML Patients <60 years:chemotherapy with an anthracycline and cytarabine or methotrexate
Patients >60 years:
palliative anthracycline, cytarabine or mitoxantrone
If M3 type AML, i.e. acute promyelocytic leukaemia (APML), then add all-trans retinoic acid to the therapeutic regime
CML
Imatinib
Patients <60 years may be considered for allogeneic stem cell transplantation Other treatments include alpha-interferon, vincristine, prednisolone, cytarabine and daunorubicin Investigations
•
Bloods: FBC, WCC, platelets, U&Es, LFTs, ESR, CRP.•
Bone marrow biopsy, lymph node biopsy.•
Radiology: X-ray, ultrasound scan, CT scan, MRI.•
AML and ALL are classified using the French–American–British (FAB) classification.Complications
•
Death.•
Increased risk of infection.•
Haemorrhage: pulmonary, intracranial.•
Depression.•
Complication of chemotherapy. MAP 6.4 Leukaemia Chapter_06.indd 101 08/12/14 6:16 PMHaematology
102 Map 6.5 Hodgkin’s vs. Non-Hodgkin’s Lymphoma
HODGKIN’S LYMPHOMA