Thursday, March 10, 2011

Leukostasis and thrombosis in CLL

The highest white count that I have seen in CLL is 800,000/cu mm though Tom Kipps told me of a patient with 1,400,000/cu mm. The odd thing is that neither of us has ever seen leukostasis in CLL. This is the condition, often seen in myeloid malignancies where sludging of white cells in blood vessels cuts off the circulation to a particular organ. Commonly, the eye or the brain is involved, causing blindness or stroke, but occasionally it is the penis, leading to priapism. It is one of the reasons for using leukapheresis as a treatment.

Can it occur in CLL? There are very few case reports dealing with chronic lymphocytic leukemia (CLL) and hyperleukocytosis that have been reported in the medical literature. This case was described in 2002 in Leukemia Lymphoma. Cukerman et al described a 73-year-old woman who presented with newly diagnosed CLL, leukostasis, and a white count of 2,000,000/cu mm, affecting the respiratory and nervous system. She responded to leukapheresis followed by chemotherapy. In addition, she also had deep vein thrombosis (DVT).

Deep venous thrombosis usually occurs in the leg and is dangerous because it is the commonest source of pulmonary emboli and these may be fatal. If the thrombosis is confined to the calf it seldom causes more than local trouble, but if it extends above the knee, anticoagulation is necessary to prevent a piece of thrombus breaking off and traveling via the heart to the lungs. The other problem that can arise following venous thrombosis is swelling of the legs. Although veins heal up and become patent again, they lose the valvular mechanism that allows us to sustain a tall column of blood without fluid spilling through the capillaries into the tissue. This is why it is sensible to wear a support stocking for at least a year after a DVT and possibly permanently.

Are DVTs commoner in CLL than in the general population? A paper has just appeared in the journal I edit (Leukemia Research) which looks at this question. (Annika M. Whittle,David J. Allsup and James R. Bailey Chronic lymphocytic leukaemia is a risk factor for venous thromboembolism Leukemia Research 35:419-421 March 2011.)

The reported incidence for venous thromboembolism (VTE) in the general population is around 0.15–0.2% per patient year in adults, with two- to threefold higher rates in the over 60-year olds. In an unselected lymphoma population the incidence is much higher at 6.4%

Whittle et al have 268 patients with CLL on their books with a median duration of follow up of 5.4 years. They act as a referral center in north-east England for a population of 1.1 million. In a retrospective survey they identified from hospital records all cases of VTE identified both among CLL patients and others. There were 15 cases of VTE among 14 patients (5.22%). The incidence per patient year of follow up was 1.45%. Many of the patients had other risk factors for VTE including obesity (2) immobility (3), acute infection (3), a recent airplane flight (1) and enlarged lymph nodes in an appropriate area (2). 7 of the VTE events occurred in Binet stage C patients who represented a minority of patients. One patient probably had thrombophilia since she had had a history of DVTs and pulmonary emboli throughout her life before she developed CLL. None of the patients had a formal thrombophilia screen. All bar 2 of the patients were over-60.

The annual incidence of VTE in this group of patients was 3-10 times higher than that of the general population but only about a quarter of that of the lymphoma population. It was not related to the height of the white count but was associated with more advanced disease. The incidence may be biased by over-observation since CLL patients are more iintensely observed than the general population, and DVTs are often missed in general practice, especially in older people.

Doctors should be aware that CLL patients are at greater risk for DVT than the general population, but at 1.45% a year they are not going to see many cases.


Anonymous said...

Thank you for the article. Does the taking of a low dose aspirin reduce the incidence of DVT?

Terry Hamblin said...

Probably not.

Anonymous said...

Very interesting. Could you please clarify which lymphomas you are referring to when you note that patients with CLL had half the rate of VTE as those with lymphoma?

Anonymous said...

A further question, in the lymphoma group, did the VTE result from leukostasis?

Terry Hamblin said...

The lymphomas were unselected, which means that they included mainly follicular lymphoma and diffuse large B cell lymphoma, but they may have incuded other sorts. ANd the incidence in CLL was a quarter of that of lymphomas, not a half.

Terry Hamblin said...

No. Leucostasis only occurs where there is a leucocytosis which would be unusual in lymphoma.