Case 1

A 14 year old boy presented at the Paediatric Emergency Department complaining of pain and swelling in his right lower leg. Prior to arriving at the Emergency Department, he had been on outpatient antibiotic treatment for infection. He was admitted to hospital and placed on low molecular weight heparin for a suspected Deep Vein Thrombosis (DVT). On day 5 after admission the patient felt dyspnea and pain in his left thorax and he was diagnosed with a pulmonary embolism (PE).

The patient’s personal and family history revealed he was an only child, while his mother had subsequently suffered a spontaneous abortion with a later pregnancy. His paternal grandmother had suffered a cerebrovascular event and his maternal grandparents were both cardiovascular patients. There was no family history of DVT in young relatives.

Laboratory analyses showed the following values:
Patient                                 Normal Range
C-Reactive Protein (CRP) (mg/L)                                           21.1                                         0.1-2.8
Leucocytes (x109/L)                                                                  12.6                                         4.4-11.0
Platelet Count (x109/L)                                                            90                                            180-450
Fibrinogen (g/L)                                                                        5.3                                             1.8-3.5
D-dimer (mg/L)                                                                         1.3                                             <0.3
FXIII (%)                                                                                     50.6                                          70-120
Protein S (%)                                                                              50.1                                           70-120
PAI-1 (IU/ml)                                                                            4.9                                             0.3-3.0

All other clotting factors were within normal ranges.

Genetic testing for polymorphisms known to be hereditary thrombophilic factors showed the following genotypes:

Factor V Leiden G1691A                                                         G/G (wild type)                        G/G (wild type)
PAI-1 4G/5G                                                                                       4G/5G                            5G/5G (wild type)
Prothrombin mutation G20210A                                         G/G (wild type)                       G/G (wild type)
MTHFR polymorphism C667T                                             C/C (wild type)                        C/C (wild type)

Detection of Lupus Anticoagulant and Anti Cardiolipin Antibodies suggested the patient was suffering from Anti Phospholipid Syndrome (APLS).

Survey the reported laboratory findings, suggesting reasons for the observed abnormal findings and options for the patient’s future therapeutic management.

Question 2

A 35 year old woman of Chinese ethnic background (Guangdong province) presented with a near normal Haemoglobin level of 112 g/L. On performing a Full Blood Count (FBC) she was found to have an erythrocyte Mean Cell Volume (MCV) of 64.9fL and a Mean Cell Haemoglobin (MCH) value of 20.6 pg.

A family study was performed on her father, mother and younger brother, including capillary
electrophoresis. The following values were found:

Father             Mother               Brother                 Patient             Normal Range

Age                                 74                          69                           32                             35
Hb (g/L)                       98                        107                          113                            112                       133-167 (m)
118-148 (f)
MCV (fL)                      69                         89.4                       62.7                          64.9                      80-100
MCH (pg)                    22.5                      29.2                       20.1                          20.6                      28-32
HbA (%)                      98.0                      97.2                       97.8                          98.0                      97-98
HbA2 (%)                      2.0                        2.7                          2.2                            2.0                      1.5-3
RBC (x1012/L)            4.36                      3.6                        7 5.63                         5.44                    4.3-5.0 (m)
3.8-4.8 (f)
Ferritin (ug/L)           65                          63                             85                            110                      41-350

Summarise these results for each member of the family and describe features of the erythrocytes that you may expect to observe on a stained peripheral blood smear.

Provide a provisional diagnosis of the condition affecting the family, describe further laboratory tests that could be performed to confirm your diagnosis and describe potential genetic problems associated with this diagnosis.

Case 3

A 65 year old male takes advantage of a health screening service provided by his employer. He has not experienced any fevers, chills or weight loss but does remark of feeling more tired than usual for a few months.

The Full Blood Count returns the following results:

White Blood Cells            14 x 109/L
Haemoglobin                          136g/L
Haematocrit                            0.41
MCV                                          91fL
Platelets                            400 x109/L

The White Cell Differential Count shows the following values:

Percentage (%)                   Absolute Count (x109/L)
Neutrophils                               20                                                       2.8
Lymphocytes                             75                                                     10.5
Monocytes                                   5                                                       0.7
Eosinophils                                 0                                                       0
Basophils                                     0                                                       0

A peripheral blood smear stained with MGG showed the following picture:

X40 Magnification

Provide a provisional diagnosis for this patient, summarising the findings shown above and highlight the relevant features on which you have based this diagnosis. Describe further investigations which could be performed to provide additional support for your diagnosis. Discuss the prognosis for this patient and any potential therapeutic treatment that could be provided.

Case 4

Haemolytic Disease of the Foetus and Newborn (HDFN) is most commonly caused by IgG antiRhD antibodies generated in RhD negative mothers who have been immunised against RhD antigen through previous pregnancies or blood transfusion.

Your Laboratory has been sent samples from a pregnant 28 year old woman requesting a blood group and antibody screen after an ultrasound scan at 29 weeks of gestation suggested the presence of severe foetal hydrops in the foetus, a clinical feature normally associated with HDFN.

The mother’s blood group is O RhD positive. She had given birth to a single child two years earlier, who exhibited evidence of jaundice at birth. The newborn required a blood transfusion on day 3 of life and subsequently died on day 7.

Describe in detail how you would investigate this case further and describe any therapeutic measures the child may require.